An Obese Patient with Chronic Kidney Disease and Deep Vein Thrombosis (DVT). How to Monitor the Anticoagulation with Enoxaparin?

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

A 62-yo Caucasian male (CM) with a complicated past medical history (PMH), including gastrointestinal (GI) bleeding from esophageal varices, colon cancer and chronic renal insufficiency (CRI), is hospitalized with a deep vein venous thrombosis (DVT). He is obese and had a hemicolectomy 3 weeks ago.

Lovenox (enoxaparin) is started, warfarin (Coumadin) use is contraindicated due to history of gastrointestinal (GI) bleeding.

He will need anticoagulation with Lovenox (enoxaparin) for 6 months.

Is there any way to know if Lovenox (enoxaparin) dose is therapeutic? What do we check?

- factor Xa
- PTT
- PT
- anti-Xa level

You have to check anti-Xa level. This is NOT factor Xa level, which most likely will be normal with Lovenox (enoxaparin) therapy.

PTT is not useful in monitoring therapy with LMWH. PTT should be used to monitor treatment with UFH, i.e. regular IV heparin.

What is anti-Xa level? Is it some "special" factor anti-Xa?

No, there is no factor anti-Xa. There is a factor Xa, just like the other 12 factors in the anticoagulation cascade (there is no factor VI).

Anti-Xa level is determined by a simple mixing study. Patient plasma is added to a known amount of factor Xa with antithrombin. LMWH in the patient plasma will bind to antithrombin and inhibit factor Xa. The amount of residual factor Xa is inversely proportional to the amount of LMWH the plasma.

Low anti-Xa value indicates a high level of anticoagulation. High anti-Xa level indicates a low level of anticoagulation. For example, anti-Xa level of 0.5 indicates adequate anticoagulation, a level of 3 is not sufficient.


Fig 1. The coagulation cascade. Legend: Black arrow = conversion/activation of factor. Red arrows = action of inhibitors. Blue arrows = reactions catalysed by activated factor. Grey arrow = various functions of thrombin. Image source: Wikipedia, public domain.

What is the required anti-Xa level for adequate anticoagulation?

Therapeutic range:

- heparin: 0.3-0.7 units/mL
- LMWH: 0.4-1.1 units/mL for SQ q 12 hr dosing. For once daily LMWH dosing, the therapeutic range is approximately 1-2 units/mL.

Prophylaxis of DVT:

There is no defined target range for prophylaxis of DVT. When anti-Xa levels are measured, the values are lower 0.45.

How do we order anti-Xa level?


On day 2 of therapy, a blood sample should be drawn 4 hours after the SQ administration of enoxaparin.

Should we monitor anti-Xa level routinely in patients on LMWH?

No. In patients with acute DVT treated with LMWH, the guideline developers recommend against routine monitoring with anti-factor Xa level measurements.

When is anti-Xa level monitoring indicated?

Occasions in which periodic monitoring of LMWH might be considered include:
- renal failure
- obesity or underweight patients
- prolonged use
- patients at high risk for bleeding or thrombosis

Oral rivaroxaban is non-inferior to standard therapy for symptomatic pulmonary embolism (PE) and DVT (NEJM, 2012).

References

Heparin Antifactor Xa Assay - The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358, MGH.Harvard.edu.
Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy - National Guideline Clearinghouse.
Enoxaparin (Low MW Heparin) Guidelines - ohsu.edu.
Concordance of the Activated Partial Thromboplastin Time and the Anti-Activated Factor X Assay in Monitoring Unfractionated Heparin Therapy in Critically Ill Patients - Chest.

Published: 02/12/2004
Updated: 03/22/2012

Massive Lower Extremity DVT Treated with Thrombolysis

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

A 20-year-old Caucasian male (CM) is admitted to the hospital with a right lower extremity (RLE) pain for 1 week. The pain started when he was jumping on a trampoline and he thinks that he might have twisted his ankle. Two days later he noted swelling of his right leg, which is getting progressively worse.

He was admitted to a hospital and a Duplex of RLE showed a large DVT extending from the ankle to the femoral vein in the groin area. Heparin IV was started, overlapped with Coumadin 2 days later.

Past medical history (PMH)

None.

Medications

None.

Family medical history (FMH)

Father with protein S deficiency who is on Coumadin. Every time his father stops Coumadin, he gets a "mini-stroke", as per the patient's description.

Physical examination

WD/WN in NAD.
RLE: massive swelling from the right ankle to the upper thigh, with palpable pulses, warm to touch, non-pitting edema.
The rest of the physical examination is unremarkable.

What is the most likely diagnosis?

DVT due to trauma, possible hypercoagualable state due to the positive FMH.

What happened?

Five days later, the RLE pain is the same or worse, and the circumference of the leg increased despite the anticoagulation treatment.

The patient complained of some fleeting chest pain, and a CT of the chest was ordered to rule out a PE. CT scan was negative.

What do you think is going on?

The patient is at risk for developing phlegmasia cerulea dolens - massive proximal lower extremity thrombosis associated with severe symptomatic swelling or limb-threatening ischemia. Luckily, at the moment his pulses were palpable but the fact that the swelling and pain increased despite 5 days of anticoagualtion is worrisome.

What would you do?

The patient was transferred to a tertiary care center where the vascular medicine consultant recommended a vascular surgery consult. The vascular surgeon ordered systemic thrombolysis with tPA IV at the dose of 0.05 mg/kg/h over 24 hours.

What happened next?

After the thrombolysis, the RLE swelling decreased in size, pain was controlled and the patient was discharged home.

Final diagnosis

Massive Lower Extremity DVT Treated with Thrombolysis.

What did we learn from this case?

Consider thrombolysis for patients with massive LE DVT that can be limb-threatening. The thrombolytic agent can be deliver systemically (IV) or through a catheter, directly into the clot. The catheter-directed thrombolysis is the preferred treatment method.

The indications for systemic thrombolytic therapy are a massive iliofemoral DVT (especially in the case of phlegmasia cerulea dolens) and PE with hemodynamic instability.

Thrombolytic agents appear to be beneficial if given up to two weeks after DVT is diagnosed.

Bleeding is the main complication of thrombolytic therapy. When given systemically, the streptokinase leads to 3 times more bleeding episodes than the standard anticoagulation with heparin. In addition, many patients with DVT present after surgery, and the thrombolysis is contraindicated in the settings of recent surgery.

Oral rivaroxaban is non-inferior to standard therapy for symptomatic pulmonary embolism (PE) and DVT (NEJM, 2012).

References

Thrombolytic therapy in venous thromboembolism - UpToDate (pais subscription required)
Thrombolytic Therapy - eMedicine
Catheter-Directed Thrombolysis for the Treatment of Symptomatic DVT - Circulation
Venous Thromboembolism Therapy. Cleveland Clinic.
Phlegmasia Cerulea Dolens. NEJM, Volume 356:e3, January 18, 2007, Number 3.
Image source: Saphenous vein, Gray's Anatomy, 1918 (public domain).

Published: 10/01/2005
Updated: 03/06/2012

Bronchoalveolar Cell Carcinoma

82 yo AAF is admitted to the hospital for treatment of progressive exertional dyspnea. She has a chronic dry cough which has not changed recently. She denies having any chest pain or hemoptysis. She is not aware of any prior evaluation for her lungs, however review of the record indicates she has had an abnormal CT scan particularly in the right lower and right middle lobe dating back 1 1/2 years ago. Biopsies were inconclusive. She is a remote smoker.

PMH:
Severe end-stage cardiomyopathy with ejection fraction of 15%

Physical examination:
Cachectic in NAD
VS 36.8-20-76-143/80
SpO2 96% on 2L
HEENT: mild JVD
Lungs: Harsh Velcro-like rales heard on the left almost to the scapula tip with a few rales at the right base
CVS: Heart sounds are distant
Abdomen: soft, nontender
Extremities: No c/c/e

CXR showed a progression of bilateral pulmonary infiltrates, especially on the right.


Bilateral bronchialveolar carcinoma; CXR report

What it looks like high diaphragms on this CXR actually is the fluid produced by this cancer. Half of the lungs are filled with mucinous secretions. See how the trachea dives deep in the fluid - the carina is well below the fluid level.

The first biopsy done during bronchoscopy was inconclusive. The pulmonary consultant thought that the patient most likely had bronchoalveolar cell carcinoma and recommended transthoracic biopsy under CT guidance. The biopsy confirmed the clinical diagnosis.


Biopsy report

Final diagnosis:
Bronchoalveolar cell carcinoma

What happened?
The patient's lung cancer was inoperable, she refused any further treatment and soon expired under hospice care.

Surgical Procedure in a Patient with Thrombocytopenia. When to Transfuse Platelets?

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

A 67-year-old Caucasian male (CM) is admitted to the hospital with an exacerbation of Wegener's granulomatosis. CT scan of the chest shows bilateral nodules. He has a PMH of myelodysplastic syndrome with a platelet count of 11/microL. The patient is scheduled for a bronchoscopy with biopsy of the pulmonary nodules tomorrow.

What is the safe platelet count for a surgical procedure?

In general, a platelet count of 50,000/microL is adequate for most surgical procedures.


How can you increase platelet count in thrombocytopenia?

By transfusing platelets, if the patient is a candidate for such transfusions. For example, patients with immune thrombocytopenia generally do not respond well to platelet transfusions due to rapid destruction by circulating antibodies.

What is the correlation between the number of platelet units transfused and the increase in platelet count?

As a "rule-of-thumb" for most adults, transfusion of six units of platelets (a 6-pack) should raise the platelet count by 25,000/microL.Refractoriness to platelet transfusion is defined as a platelet count increment of less than 5,000.

Six pooled platelet concentrates (a 6-pack) is equivalent to one plateletpheresis concentrate.

What happened?

The patient was transfused 6 units of platelets the day before the procedure and 6 units one hour before the bronchoscopy. The procedure was completed uneventfully.

What did we learn from this case?

Platelet count of 50,000/microL is adequate for most surgical procedures. Transfusion of six units of platelets (a 6-pack) should raise the platelet count by 25,000/microL.

References

Clinical and laboratory aspects of platelet transfusion therapy. UpToDate 14.1 (paid subscription required).
Preoperative management of patients with cancer. UpToDate 14.1 (paid subscription required).
Guidelines for the Management of Platelet Disorders. University of Alabama at Birmingham
Myelodysplastic syndromes: A practical approach to diagnosis and treatment. Cleveland Clinic Journal of Medicine January 2010 vol. 77 1 37-44.

Published: 04/12/2006
Updated: 01/04/2010

Treatment of AIDS-related Neutropenia

Author: V. Dimov, M.D., Cleveland Clinic

A 40 yo AAM with end-stage HIV/AIDS has a WBC of 1.66, ANC 498, Hgb 13.7, platelets 61.

PMH:
Hypertension, HIV, h/o esophageal candidiasis, h/o HZV face

Medications:
Acyclovir, doxycycline, esomeprazole, azithromycin, dapsone, Truvada, Norvir, Atazanavir

Laboratory results:


Neutropenia and thrombocytopenia in AIDS

ID suggests starting G-CSF. Which one should you choose? Neulasta or Neupogen?

Neupogen is FDA-approved for use in AIDS neutropenia. It is given daily and the effect can be titrated, e.g. the administration can be stopped when the desired effect is achieved (ANC >1000 x3 days). Neulasta is given just once, in a single dose. In chemotherapy-induced neutropenia, a single dose of Neulasta is as effective as 16 doses of Neupogen.

In the patient described above, Neupogen is a better choice.

Granulocyte Colony-Stimulating Factor (G-CSF) is a glycoprotein growth factor which stimulates bone marrow to produce granulocytes. The recombinant human G-CSF synthesised in an E. coli expression system is called filgrastim. Filgrastim (Neupogen®) and PEG-filgrastim (Neulasta®) are two commercially-available forms of rhG-CSF (recombinant human G-CSF). The PEG (polyethylene glycol) form has a much longer half-life, reducing the necessity of daily injections (modified from source: Wikipedia).

Neupogen (Epocrates link)
filgrastim
AIDS neutropenia
1-10 mcg/kg SC qd
Check CBC baseline and 2x/wk; may D/C if ANC >1000 x3 days.

Neulasta (Epocrates link)
pegfilgrastim
Neutropenia, post-chemo
6 mg SC x1
Monitor CBC, plt

What happened?
The patient was evaluated by Hematology/Oncology who also recommeded treatment with Neupogen. ANC improved with Neupogen, the patient was asymptomatic and was discharged home with ID follow-up.

Final diagnosis: AIDS-related neutropenia

References:
Neutropenia. eMedicine.
Recombinant granulocyte colony-stimulating factor in the long-term treatment of AIDS-related neutropenias. Recenti Prog Med. 1993 Jul-Aug;84(7-8):526-30.

Created: 02/01/2007
Updated: 02/13/2008

Oral Mucositis due to Radiotherapy

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D.,

A 80-year-old CF with widespread multiple myeloma is admitted to the hospital with CC: jaw pain and not being able to eat.

Past medical history (PMH)

Myeloma, hypertension (HTN).

Physical examination

Painful left side of the jaw, limited mobility.

What is the most likely cause of symptoms?

- Lytic lesion of jaw bone due to myeloma
- Pathologic bone fracture of mandibula or maxilla

What would you do?

X-ray of mandibula and maxilla.
CT scan of the brain and facial bones.

What happened?

CT scan of the brain and facial bones showed a 2 x 2.8 x 2 cm expansile lucent area in the left body of the mandible consistent with multiple myeloma. Probable medial angulation displacement of a left-sided molar associated with the focal lytic lesion in the mandible.

What happened next?

Hem/Onc and radiation therapy consults were called and radiotherapy of mandible was recommended.

After 4 radiation treatments, patient started to complain of dry mouth and local pain. Physical examination showed mucositis. She is scheduled for a 10 treatments-course.

What is the treatment for mucositis due to radiation or chemotherapy?

Local treatment with Miracle Mouthwash" (see below).

Final diagnosis

Oral mucositis due to radiotherapy.

What did we learn from this case?

Radiation treatment interferes with the regeneration of oral epithelium resulting in mucositis. This process is painful and interferes with food intake. Chemotherapy can have a similar effect on the mucosa.

Mucositis develops in 60-70 % of patients receiving radiotherapy for head or neck malignancy.

Mucositis is treated symptomatically with oral hygiene and topical anesthetics which can be combined in a "cocktail," commonly called "Miracle Mouthwash" (lidocaine, diphenhydramine, and Maalox).

Single dose of palifermin prevents oral mucositis during chemotherapy in patients with cancer. Palifermin (trade name Kepivance, marketed by Biovitrum) is a human recombinant keratinocyte growth factor (KGF) produced in Escherichia coli. Palifermin costs approximately 5,000 Euros per treatment for a 70 kg patient.

References

Complications of radiotherapy for head and neck cancer - UpToDate (subscription required).

Palifermin Prevents Oral Mucositis During Chemotherapy in Patients With Cancer - Ann Intern Med, 2010 http://goo.gl/F7e1

Published: 06/12/2005
Updated: 09/20/2010

Anemia due to Iron Deficiency and Chronic Disease

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

A 58-year-old African American male (AAM) was admitted from a nursing home (NH) with a chief complaint (CC) of being lethargic and not acting appropriately. The patient stated that his legs hurt, and they had been hurting for a long time.

Past medical history (PMH)

Diabetes mellitus type II (DM), hypertension (HTN), venous stasis ulcers, anemia, hepatitis C, peripheral vascular disease (PVD), congestive heart failure (CH).

Past surgical history (PSH)

Bilateral lower extremity (B) LE) stasis ulcers status post (S/P) debridement and multiple failed skin grafts 2 years ago, a right hallux amputation.

Medications

Tylenol (acetaminophen), Ambien (zolpidem), hydrocodone, FeSO4, clonidine, amitriptyline, Oxycontin (oxycodone), Lantus (insulin glargine), Lasix (furosemide), metformin, Actos (pioglitazone), metoprolol.

Social history (SH)

Remote history of heroin and cocaine abuse, former smoker and drinker.

Physical examination

VS 38-126-24-137/81.
Chest: CTA (B).
CVS: tachycardic but regular with no murmurs.
Abdomen: Soft, NT, ND, +BS.
Extremities: severe venous stasis ulcers of the lower extremities (B).
Neuro: AAO x 2. No focal neurological deficits apart from diminished sensation on (B) LE.


A diabetic patient with (B) infected stasis ulcers.

What laboratory workup would you order?

CBCD, CMP, UA.
Wound culture, BC x 2.
X-rays.

CBC in iron deficiency anemia (IDA) (left, click to enlarge the image); CMP, hypogycemia was corrected; CBCD, iron profile and prealbumin.

Iron and iron saturation were low but the ferritin was high and the TIBC was low. What was the reason?

A combination of iron deficiency anemia and anemia of chronic disease.

BUN was 51 mg/dL and creatinine 2.5 mg/dL. Hemoglobin was Hgb 8.8 mg/dL.

What questions would you ask? What are his baseline laboratory values?

A review of his previous medical records showed a BUN of 14 mg/dL and creatinine of 1.3 mg/dL seven months ago.

WBC was 17.1/mm3, hemoglobin 8.8 mg/dL, hematocrit 26.7, and hypochromic, microcytic peripheral smear. The differential count showed 69% neutrophils and 11% bands.

The patient most likely had an infection, and was volume depleted which could explain the rise in the BUN/Cr. His mucosal membranes were dry.

What happened?

The patient was admitted to a telemetry unit. Zosyn (piperacillin and tazobactam) and IV fluids were given.

His hemoglobin decreased to 7.6 mg/dL on the day after admission.

What do you think is the reason for the "drop" in hemoglobin?

Mainly hemodilution -- see the input and output summary over the last 24 hours (I/O) below. The patient was with a 3-L positive balance.


I/O showed that the patient was 3 liters positive.

The patient was transfused 2 units (U) pack red blood cells (PRBC), and iron profile and ferritin were ordered as add-on tests.

The iron profile showed severe iron deficiency bu why ferritin was high?

The patient had wound infection and this could be the reason for the high ferritin and platelets. TIBC was low because he also had anemia of chronic disease.

Note how the BUN and Cr returned to baseline values with the volume replacement with IV fluids (see the laboratory results above).

What is the cause of iron deficiency anemia? Is he bleeding?

The patient was hemodynamically stable -- stable vitals signs (VSS) and without orthostatic changes. The rectal exam showed brown stool, negative for occult blood and the H/H was stable. The admitting team decided that the patient's anemia was unlikely to be secondary to acute GI bleeding.

There are several causes for iron deficiency anemia that can be remembered by the mnemonic NIMBLE:

Need -- increased need as in pregnancy, children during stages of rapid growth, etc.
Intake is low, e.g. in malnutrition
Malabsorption
Blood
Loss, e.g. GI bleeding
Excessive donation, e.g. in blood donors

What happened to this patient?

His prealbumin was very low - 9.2. The most likely reason for iron deficiency anemia was malnutriton due to poor PO intake.

The patient received 2 U PRBC. A blood conservation protocol was started with iron and Epogen (epoetin alfa). A nutrition consult was called.

Final diagnosis

Iron deficiency anemia (IDA) secondary to malnutrition. Anemia of chronic disease.

What did we learn from this case?

The most dangerous cause of iron deficiency anemia is GI bleeding and it needs to be ruled out first.

Consider poor PO intake in the differential diagnosis of iron deficiency anemia, especially in the debilitated patients with multiple comorbidies.

A decrease in the hemoglobin can be due to hemodilution. This is especially true in hypovolemic patients with preexisting anemia. The rule of thumb is that one liter of IVF can decrease the hemoglobin by as much as one gram/dL.

Use the blood conservation protocol early. Giving blood has the disadvantages of being expensive and exposing patients to infections.

References

Iron Deficiency Anemia. Marcel E Conrad. eMedicine, 2006.
Iron Deficiency Anemia. American Academy of Family Physicians, 2007.
Normocytic Anemia. American Academy of Family Physicians, 2000.
Anemia in the Elderly. American Academy of Family Physicians, 2000.
Anemia, Chronic. Fredrick Melik Abrahamian et al. eMedicine, 2008.

Published: 06/01/2004
Updated: 02/01/2009

Iron overload due to blood transfusions in sickle cell disease

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

A 29-year-old African American male (AAM) with a known history of sickle cell disease and multiple blood transfusions was admitted through the ER with symptoms consistent with his prior sickle cell crises. He complained of pain in his knees, hips, and back that had been "off and on" for the last couple of months. It became markedly worse this afternoon and began to involve his chest and his arms. He denies fevers, chills, rigors, or night sweats.

Past medical history (PMH)

Sickle cell disease, aseptic necrosis of bone (hips and back).

Medications

Hydroxyurea, gabapentin, methadone, deferasirox, folic acid, multivitamin (MVT).

Family medical history (FMH)

Mother, father and brother with sickle cell trait.

Physical examination

Stable vital signs (VSS).
Eyes: anicteric.
ENT: Oropharynx clear, no plaques or exudates.
Respiratory: clear to auscultation bilaterally, no respiratory distress, no rales, no rhonchi, no wheezing.
Cardiovascular: no murmurs, no rubs, no gallops, regular rate and rhythm.
Gastrointestinal: soft, nontender, nondistended.
Genitourinary: no CVA tenderness
Extremities: no c/c/e.

What is the most likely diagnosis?

Sickle cell crisis.

What diagnostic tests would you suggest?

CBC
Reticulocyte count
CMP
CXR
UA

What happened?

CBC showed anemia with evidence of iron overload from previous ferritin measurements.


Figure 1. CBC in sickle cell anemia (click to enlarge the image).


Figure 2. Increase in ferritin level secondary to blood transfusions in a 29-year-old patient with sickle cell disease (click to enlarge the image).

Sickle cell crisis resolved with pain medications, NS at 100 cc/hr and O2 via NC. The patient received 2 U PRBC. CXR was negative for acute chest syndrome and UA was negative for infection.

Deferasirox (Exjade), an oral iron chelator, was continued.

Final diagnosis

Chronic iron overload due to blood transfusions in sickle cell disease.

Summary

There is no specific hemoglobin number which triggers blood transfusion. Iron overload is a significant problem for patients with sickle cell disease who commonly have a ferritin level of 3,000. Many patients are able to tolerate a hemoglobin level in 6-7 mg/dL range without adverse symptoms.

Related reading

Sickle Cell Anemia Centenary: the article "Peculiar elongated and sickle-shaped red blood corpuscles" published in 1910 http://goo.gl/SAg54

Published: 09/13/2007
Updated: 02/01/2010

Warfarin (Coumadin)-Induced Skin Necrosis

Author: V. Dimov, M.D.
Reviwer: S. Ramdhawa, M.D.

A 51-year-old African American female (AAF) was admitted to the hospital with a chief complaint (CC) of  shortness of breath (SOB) for 1 week and and pain in the right thigh x 3 weeks. The SOB was not getting better with the aerosol treatment. She also complained of occasional orthopnea and paroxysmal nocturnal dyspnea (PND). The right thigh pain started 3 weeks ago, in the medial part of the right thigh, throbbing in nature, associated with redness. The patient complained of swelling in the same region which had progressed over the the past few days. She denied fever or chills.

Past medical history (PMH)

Asthma, congestive heart failure (CHF), diabetes melitus (DM), anemia, pancreatitis, hypertension (HTN), shingles.

Past surgical history (PSH(

Cholecystectomy, thyroidectomy.

Medications

Prednisone, Lasix, Synthroid, Norvasc, K-Dur, Diovan, Percocet, aerosols, Advair, Singulair, Flonase, Nexium, Neurontin

Family medical history (FMH)

Diabetes melitus (DM), hypertension (HTN).

Physical examination

Obese lady in NAD
VS 36.7- 88-18-176/95 SpO2 95% on RA
Chest: (B) wheezing
Heart: Clear S1S2
Abd: Obese, NT, +BS
Ext: (B) 3+ edema, right thigh was swollen, erythematous and tender. Peripheral blood vessels could not be felt in the lower extremities because of the edema.

What happened?

BNPep was 10, and D-dimer was 7000. The Duplex of LE showed a RLE DVT.

She was admitted for asthma exacerbation and DVT in her right extremity. Patient was started on heparin IV and then later on switched to Lovenox. Coumadin was started within 48 hours.


CBC, BMP, INR; Anticoagulant treatment time frame (click to enlarge the images).

What happened next?

Two days after starting Coumadin, the patient developed ecchymoses over her lower abdomen and upper extremities. Small black eschars appeared in the center of some of the ecchymoses with a "halo" around the lesions. These skin lesions were completely asymptomatic - no pain or itching.

Coumadin-induced skin necrosis was diagnosed and Coumadin was stopped. Lovenox 1 mg/kg SQ QD was continued for 2 days, then IVC filter was placed and Lovenox was stopped. She did not have any new lesions.


Coumadin-induced skin necrosis (click to enlarge the images).

Final diagnosis:

Warfarin (Coumadin)-induced skin necrosis.

What did we learn from this case?

Coumadin-induced skin necrosis can occur in DVT patients when oral anticoagulation is started, despite the heparin coverage.

The classic large necrotic areas seen in the textbooks occur in patients treated with Coumadin only (without heparin). In real life, when heparin us used, the skin necrosis areas are often much smaller in size, like in our patient.

Oral rivaroxaban is non-inferior to standard therapy for symptomatic pulmonary embolism (PE) and DVT (NEJM, 2012).

References

Dermatologic Manifestations of Hematologic Disease. eMedicine.
Coumadin Skin Necrosis. Boston University.
Coumadin-Induced Skin Necrosis. Medscape, 11/12/2002.
Heparin-Induced Skin Necrosis - NEJM Volume 335:715, September 5, 1996, Number 10.

Published: 06/01/2004
Updated: 04/05/2012

Thrombocytopenia due to Kasabach-Merritt Syndrome

Authors: A. Kumar, M.D., V. Dimov, M.D., The Cleveland Clinic

An one-year old boy presented to the hospital with right upper arm swelling since birth (click to enlarge the picture) and a low platelet count done by the primary care physician. No other skin lesions were found. CT of the chest and abdomen were negative.

The child has had a normal development.

Steroids were started for suspected immune thrombocytopenia (ITP) but despite a 10-day course the platelet count went down to 1,500.

PMH:
RUE hemangioma

Medications:
None


Fig. 1: Hemangioma of right upper arm

What do you think is going on?
The boy has a hemangioma and thrombocytopenia. Kasabach-Merritt syndrome presents with this combination of symptoms.

What would you do?
Confirm platelet count.
Consult pediatric hematology and vascular surgery.

What happened?
The pediatric hematologist recommended a trial of Vincristine to shrink the hemangioma. The vascular surgeon recommended embolization of the hemangioma if there is no effect from Vincristin therapy.

Final Diagnosis:
Kasabach-Merritt syndrome

What did we learn from this case?
Suspect Kasabach-Merritt syndrome in patients with hemangioma and thrombocytopenia. Thrombocytopenia is caused by sequestration and destruction of platelets in a large cavernous hemangioma. The syndrome is usually seen in infants but can also be rarely observed in adults.

No single treatment approach is consistently effective.

References:
Kasabach-Merritt Syndrome. eMedicine, topic 1234.
Kasabach-Merritt Syndrome. eMedicine, topic 1221.

Related:
Propranolol for Severe Hemangiomas of Infancy. NEJM, 06/2008.

Published: 03/09/2006
Updated: 06/14/2008

Ocular Manifestations of Systemic Disease

Links via RedAtlas.org, Alexander Walsh, MD, 2002. Click on the links below to see the images.

Retinal nonspecific signs

Cotton wool spots

Intraretinal hemorrhages

Choroidal neovascularization

Ophthalmic signs of specific conditions

Cotton wools spots and flame hemorrhages in hypertensive retinopathy

Proliferative diabetic retinopathy

Hollenhorst plaques

Uveitis in rheumatoid arthritis

Giant cell arteritis

Wegener's granulomatosis affecting the anterior eye segment

Uveitis in ankylosing spondylitis

Thyroid eye disease

Roth spots

Cytomegalovirus retinitis

Ophthalmic conditions of relevance to the internist

Glaucoma

Cataract

Retinal detachment

Image source: Wikimedia Commons.
Updated: 06/01/2007

Suspected deep vein thrombosis (DVT) - to treat or not to treat?

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

A 69-year-old Caucasian male (CM) with a past medical history (PMH) of diabetes mellitus type 2 (DM 2), atrial fibrillation (Afib) on warfarin (Coumadin), and hypertension (HTN) was admitted to the hospital with a chief complaint (CC) of left leg pain. Cellulitis was diagnosed and the antibiotic Unasyn (R) was started. During the hospital stay, the patient was found to have anemia with Hgb 8 mg/dL and guaiac positive stools. A colonoscopy showed diverticulosis and a benign polyp which was removed. Warfarin (Coumadin) was held for 10 days. He was on heparin 5000 U SQ BID.

Why are we presenting this case?

Read on... it will become interesting. An X-ray of the left heel showed osteomyelitis and patient was scheduled for surgery. At the same time, the left calf swelling was not subsiding although patient was afebrile and the WBC was normal (WNL). The d-dimer was 2117, and INR was 1.10.

Does he have deep vein thrombosis (DVT)?

The d-dimer may be elevated due to a lot of different reasons and is not specific for DVT. A left calf DVT was suspected and confirmed by the preliminary Duplex report. Full dose enoxaparin (Lovenox) was started at 1 mg/kg q 12 hrs.

During the second day of LMWH therapy, the patient developed rectal bleeding, passing clots.

How to treat bleeding caused by LMWH?

FFP
is not helpful and Protamine is effective in only 50-70% of cases. This is one of the drawbacks of LMWH therapy.

What happened?

Enoxaprain (Lovenox)
was stopped and bleeding gradually resolved. Hgb was stable around 8-9 and he did not need PRBC transfusion. A tagged RBC scan did not show any evidence of acute bleeding.


NM GI Bleeding scan (click to enlarge the image).

The final Duplex report was not convincing of DVT.


Venous Duplex Report-LLE (click to enlarge the image).

What to do now?

Nuclear medicine venous thrombosis scan with TC 99 Accutect, i.e. Accutect scan.
Accutect did not show an acute DVT.


NM Accutect scan for DVT (click to enlarge the image).

Follow-up

The patient had a persistent AFib and the rate was controlled. For now he will be on Plavix and ASA. His anticoagulation with Coumadin (very risky given the history) will be discussed with the GI and Cardiology consultants.

What did we learn from this case?

Anticoagulation
is risky. Starting Coumadin for someone with DVT opens a whole new bag of worms and changes their life for at least 6 months. It is not an easy decision to make and that's why we have to be sure. If the Duplex is not conclusive you have to do an Accutect scan.

Oral rivaroxaban is non-inferior to standard therapy for symptomatic pulmonary embolism (PE) and DVT (NEJM, 2012).

References

Phlegmasia Cerulea Dolens. NEJM, Volume 356:e3, January 18, 2007, Number 3.

Related reading

Cheney treated for blood clot in his leg. CNN, March 5, 2007.

Published: 04/06/2005
Updated: 04/05/2012

Fatigue for One Month due to Severe Anemia. What is the Cause?

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

A 76-year-old African American female (AAF) was admitted to the hospital with a chief complaint of fatigue for one month, and shortness of breath (SOB) and dyspnea on exertion (DOE) for one week.

The patient denied abdominal pain, nausea, vomiting, diarrhea, constipation (N/V/D/C), hematemesis, melena or hematochezia. She denied use of NSAIDs or anticoagulants. No paroxysmal nocturnal dyspnea (PND), chest pain (CP) or cough.

She was hospitalized with acute GI bleeding 6 months ago and she had both upper and lower endoscopies at that time. The upper endoscopy showed an angiodysplasia of the the duodenum that was treated with bipolar electrocoagulation. The colonoscopy showed diverticulosis but an adequate visualization of the cecum was not obtained due to the presence of a moderate amount of blood in the cecal pouch. A small bowel capsule endoscopy was canceled as the patient's stool was guaiac negative and she had no more symptoms.

Past medical history (PMH)

Mitral valve repair with metallic prosthesis, currently taking Coumadin, angiodysplasia of the of the duodenum, diverticulosis, HTN, PVD, CAD S/P CABG, RA, 5 cm AAA identified 6 months ago.

Medications

Digoxin, FeSO4, Lasix (furosemide) 40 mg po qd, Imdur (isosorbide mononitrate) 30 mg po qd, Protonix (pantoprazole) 40 mg po qd, Coumadin (warfarin) 3 mg po QD.

Allergies

Sulfa, atorvastatin (Lipitor), simvastatin (Zocor), ipratropium (Atrovent) and penicillin.

Physical examination

VS 36.7-78-16-131/63.
Pale conjunctivae.
Chest: CTA (B).
CVS: 2/6 systolic murmur at LSB, metallic click.
Abdomen: Soft, +BS, NT.
Rectal exam: brown stool, sent for fecal occult blood testing (FOBT).
Extremities: no edema.

The finding of pale conjunctivae is significant because the hemoglobin (Hgb) is usually below 8 mg/dL before we can see it. CHF is less likely with clear lungs and no leg edema on physical examination.

What is your differential diagnosis of the very vague chief complaint of fatigue?

There is a useful mnemonic for differential diagnosis of fatigue: FATIGUED

Failure (CHF)
Anemia
TU (malignancy)
Infection, e.g TB
GI cause, e.g. malabsorption
Uremia
Endocrine, e.g. DM, hyothyroidism
Depression

What is the most likley diagnosis?

Congestive heart failure (CHF) exacerbation?
GI bleed?
Anemia?

What laboratory workup would you order?

CBC (complete blood count)
CMP (complete metabolic panel)
INR (she is on Coumadin (warfarin)


Laboratory results (click to enlarge the image): WBC 6900/mm3, Hgb 5.7 mg/dL, Hct 19, MCV 74 fl, MCH 22, platelets 347,000/mm3.

INR was elevated to 2.29. PTT 47.

The patient's indices were consistent with microcytic, hypochromic anemia. The iron profile showed severe iron deficiency anemia.

Reticulocyte count was 3.9

The stool guaiac test came back positive.

What is the etiiology of the anemia?

The most likely etiology of the patient's anemia is iron deficiency (IDA) likely secondary to a chronic GI blood loss due to angiodysplasia involving the small bowel and possibly the colon.

What would you do?

Type, cross and transfuse 2 units of packed red blood cells (PRBC) immediately.

She has CAD and even people with normal coronaries can have cardiac ischemia of Hgb falls below 5 mg/dL.

Would you give vitamin K to reverse anticoagulation?

There was no evidence of acute bleeding. Coumadin was held.

What happened?

She was transfused to maintain a hematocrit of at least 30%.

Coumadin was stopped, and since she did not have an active bleeding, heparin was started for anticoagulation (tha patient had a metallic heart valve).

An EGD and colonoscopy were done and did not show any source of bleeding (heparin was stopped 6 hrs before the procedure).

What would you do next?

The next step was a capsule enteroscopy which revealed an AVM if the small bowel.


Medications given during the hospital stay (click to enlarge the image).

Final diagnosis

Fatigue due to severe anemia secondary to a chronic low-grade GI bleeding.

What did we learn from this case?

Fatigue and SOB are common presenting symptoms of severe anemia. Even if PMH is suggestive of CHF, think about other causes.

Anticoagulation in a patient with history of AVM or diverticulosis can be difficult. These patients need anticoagulation for their valve (or any other reason) but a major GI bleed may kill them. Sometimes the only solution is total colectomy in cases of diverticulosis with recurrent bleeding.

Published: 06/11/2004
Updated: 01/19/2009

INR 17 and Hematuria: What To Do?

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

Clinical Case 1

A 32-year-old African American male (AAM) is admitted to the hospital with a chief complaint (CC) of hematuria and back pain for 2 days.

He is on warfarin (Coumadin) 15 mg daily for a pulmonary embolism (PE) in the past. He has not had his INR checked for the last 2 months.

What is your clinical suspicion at this point?

He may be overanticoagulated with INR as high as his warfarin (Coumadin) dose (15 mg daily).

What is the cause of his back pain?

The lower back pain may be due to a back sprain but may also secondary to a retroperitoneal hematoma

What is the hematuria cause?

Hematuria is most likely due to warfarin (Coumadin) overdose.

What laboratory tests would you suggest?

Check INR/PTT
CBCD, CMP
CT abdomen

Laboratory results

INR 11
CT abdomen: no retroperitoneal hematoma


The laboratory results revealed INR of 11 (click to enlarge the images).

How much vitamin K to prescribe for therapy in this case?

The patient refused SQ or IV injections.
Vitamin K 5 mg PO x 2 was given.

How long does it take for vitamin K to decrease INR?

Vitamin K usually acts within 6 hours. This is the reason why you should check INR q 6 hrs until a desired level is reached, after you give vitamin K IV.

What happened?

The repeated INR was 1.6.
Hematuria stopped, and back pain resolved. The patient left against medical advice (AMA), realizing the risks involved if he does not follow up on his condition with a physician.

What did we learn from the case?

Vitamin K generally works fast. You have to use it with caution in patients who need anticoagulation because it can induce warfarin (Coumadin) resistance. This patient needed vitamin K because of hematuria.

Clinical Case 2

A 65-year-old African American male (AAM) with a complicated past medical history (PMH) of diabetes type 2 (DM 2), peripheral vascular disease (PVD S/P L AKA), coronary artery disease (CAD), AFib, hypertension (HTN), chronic renal insufficiency(CRI) was taking warfarin (Coumadin) 15 mg PO daily for AFib.

He had his INR checked today and the lab technician called the PCP office informing him that the patient's INR was 7. The attending asked the patient to come to the hospital as a direct admission.

When we checked our computer system the INR was actually higher than 17 (so high that it was outside the limits of the test) rather than 7 !!!


The laboratory results showed INR of 17 (click to enlarge the images)

What would you suggest at this point?

Repeat the test?
Repeated INR was 16.30 with PTT geater than 100.

That was confusing. Is it DIC?
No. Platelets were normal.

How would you treat such a patient?

Prescribe vitamin K 10 mg PO x 1.

This is faster than the FFP 4 U x 1, which he also received.

Then, check INR q 6 hrs. Type and screen 2 U PRBC, just in case there is excessive bleeding.

What happened?

The repeated INR 8 hours later was 2.99.

This an example of another therapeutic success for Vit.K. Hematuria resolved.

What did we learn from this case?

Always check the labs yourself. Do not rely on a telephone (mis) communication.

Vitamin K is effective and it works well when taken PO. There is rarely need for IV administration. Avoid giving too much vitamin K because it will induce Coumadin resistance.

According to a recent meta-analysis, oral and intravenous vitamin K are equivalent for treatment of excessive anticoagulation. Subcutaneous vitamin K is inferior to oral and intravenous vitamin K and is similar to placebo at 24 hours after administration.

References

Warfarin: The Asymptomatic Patient with an Elevated INR. Roberts, James. Emergency Medicine News:Volume 29(2)February 2007, p 13-16.
Warfarin Therapy: Evolving Strategies in Anticoagulation. AFP 1999.
Treatment of Excessive Anticoagulation With Phytonadione (Vitamin K). A Meta-analysis. Arch Intern Med. 2006;166:391-397. Link via Notes from Dr. RW
Managing a high international normalised ratio. BMJ 2011; 341:d251 doi: 10.1136/bmj.d251 (Published 19 January 2011).

Published: 02/11/2005
Updated: 04/04/2010

Platelets Are Just 1,000 - What To Do?

Author: V. Dimov, M.D., Assistant Professor, University of Chicago
Reviewer: S. Randhawa, M.D.

A 44-year-old African Americal male (AAM) with a past medical history (PMH) of HIV/AIDS, non-compliant with his Highly Active Antiretroviral Therapy (HAART), was admitted with upper gastrointestinal (GI) bleeding to the intensive care unit (ICU).

Initially, his hemoglobin (Hgb) was 5.9 mg/dL and he was transfused 2 units of packed red blood cells (2 U PRBC). His platelet count came back as 1/mm3.


Platelet count = 1/mm3 (click to enlarge the image).

What would you do?

He was transfused with 10 untis of platelets with little effect: Platelet count increased to 4/mm3. There were petechiae on the soft palate but no other evidence of bleeding.

No GI specialist would be willing to do an esophagogastroduodenoscopy (EGD) with a platelet count of 1/mm3. The patient was "lucky" that the bleeding stopped on its own.

He gradually developed oral petechiae and mild mucosal bleeding.

How was his platelet count before this admission?

When we asked the patient if he was ever told that his platelet count was low, he answered that it was "always OK." The ID specialist checked with the HIV clinic that was following the patient and they told us that his platelets were never above 10 .

Why are the platelets low?

The HemOnc consultant made the diagnosis of idiopathic thrombocytopenic purpura (ITP), and prednisone 1 mg/kg PO QAM was started. HIV can cause thrombocytopenia as well.

What if the platelet count does not increase?

If prednisone is ineffective, you have to start IVIG, or even better, anti-Rh Ab.

Should we do splenectomy without a bone marrow biopsy in ITP?

No. Splenectomy will help only if the bone marrow is working. ITP is a clinical diagnosis. You do not need antiplatelet antibodies to make the diagnosis.

However, a bone marrow biopsy is recommended in this patient. If he has ITP, the biopsy will show a lot of megakarioblasts because the bone marrow is working hard to produce the platelets which are destructed in the periphery. On the other hand, if the thrombocytopenia is due to bone marrow failure (i.e. not ITP), the splenectomy will be useless.

In this particular patient the reticulocyte count was 6% which indicated a good BM response.

Is anti-Rh Ab better than IVIG for treatment of ITP?

Anti-Rh antibody is more effective and is also less expensive. Win-Rho (anti-Rh Ab) cost is 1/3 of the cost of IVIG. Actually, it more cost effective to do a splenectomy rather than to give IVIG.

How does anti-Rh (anti-D) work?

Anti-D antbody can be used only in Rh-positive patients. Out patient's blood group was B positive.

Antibodies cover the RBCs and when they go to the spleen, they keep the Fc receptors there "busy," thus preventing the spleen from destructing platelets. The problem is that anti-D Ab can cause hemolytic anemia, therefore its use is relatively contraindicated in patients with severe anemia.

What happened?

The patient refused a bone marrow biopsy. His platelet count increased to 7 and then drecreased again to 1 while taking Prednisone.

He developed hematuria and further oral mucosa bleeding.

12 units of platelets were transfused and IVIG was started. He refused his anti-HIV medications and left the hospital AMA.

What did we learn from this case?

It is always good practice to believe your patient but always double check the information they provide.

Examine the oral cavity of patients with thrombocytopenia daily. This is where the bleeding often first starts.

References

Immune Thrombocytopenic Purpura - Let the Treatment Fit the Patient. NEJM 8/03
Initial Treatment of ITP with High-Dose Dexamethasone. NEJM 8/03
ITP. eMedicine
Systematic Review: Efficacy and Safety of Rituximab for Adults with Idiopathic Thrombocytopenic Purpura. Annals of Int Med, 2 January 2007, Volume 146 Issue 1, Pages 25-33.

Related Reading

FDA approves Amgen's blood platelet booster (Nplate, romiplostim). Reuters, 08/2008.
Immune thrombocytopenia: No longer ‘idiopathic’ http://goo.gl/z2Ks0
Immune Thrombocytopenia - 2010 Review in Hematology http://goo.gl/tXT2U
Primary Immune Thrombocytopenia - NEJM http://goo.gl/vSr08
Immune thrombocytopenia in adults: An update. CCJM, 2012.

Published: 03/11/2005
Updated: 08/22/2011

What is the Cause of Thrombocytopenia?

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

A 62-year-old African American female (AAF) with a past medical history (PMH) of metastatic pancreatic cancer went for her regular chemotherapy course today and was found the have a low platelet count of 23/mm3. She has a history of recurrent deep vein thrombosis (DVT) despite being on warfarin (Coumadin) with a therapeutic INR of 2.9. She has been on enoxaprain (Lovenox) for DVT prophylaxis for 3 weeks.

Past medical history (PMH)

The patient had a left thigh pain 7 months ago and was diagnosed with DVT. She was started on warfarin (Coumadin) and despite a therapeutic INR, she developed a second DVT one month later. She was admitted and a CT of the chest was done to rule out pulmonary embolism (R/O PE). The CT showed a cystic mass below the left diaphragm. Adenocarcinoma of the pancreas tail with extension to the spleen was found on the explorative laparotomy. The patient has been on chemotherapy since then, for 6 months. Her C-19-9 level was initially high (44) but the went down to 8.


C-19-9 levels (click to enlarge the image).

Her platelet count was 400/mm3 one month ago. Enoxaparin (Lovenox) was started and 2 weeks later, the platelet count decreased to 200/mm3. Several days later the platelet count was just 23/mm3.

She reported a mild nosebleed the day before the admission and bleeding gums when tooth brushing for 2-3 days.

What is the most likely diagnosis?

Heparin Induced Thrombocytopenia (HIT) vs. platelet clumping.

The patient has Trousseau syndrome, therefore she needs anticoagulation. Unfortunately, warfarin (Coumadin) is effective in only 9-19% of these patients. The best solution for home use is probably enoxaparin (Lovenox) SQ. However, enoxaparin can cause HIT.

There are 2 forms of HIT:

- Type I starts within 5 days of heparin treatment and the platelet count is above 100/mm3
- Type II starts after 5-10 days of heparin treatment and the platelets is below 100/mm3

What type of management would you recommend?

- Repeat CBC
- rder antiplatelet antibodies (HIT antibody panel is the common name of the test)

Start argatroban for suspected HIT. Patients with HIT have an increased risk for both bleeding and thrombosis. Argatroban is a thrombin inhibitor than prevents thrombosis in HIT.

What happened?
6U of platelets were transfused. The tepeat platelet count showed an increase to 123.


HIT vs. chemotherapy-induced thrombocytopenia (click to enlarge the image).

Argatroban was already started and PTT was adjusted to 50-70s. INR increased to 2.24 but fibrinogen was 325 and FSP less than 5.

Final Diagnosis

Chemotherapy-induced thrombocytopenia. The condition was lower on the differential diagnosis list initially because patient was already receiving the same chemotherapy for 6 months.

Argatroban was stopped and enoxaparin (Lovenox) was restarted.

What did we learn from this case?
Always repeat the CBC when low platelet count is found. If the platelet count increases after a platelet transfusion (always a six-pack = 6U) this often rules out an immune process such as ITP or HIT.

HIT is a clinical diagnosis. You do not have to wait for result of the platelet antibody test because the test may take significant amount of time and treatment is of essence.

You have to stop ALL forms of heparin in HIT. It usually takes more than a week for the platelets to increase.

Argatroban is the drug of choice for HIT.

When to transfuse platelets?
If platelet count is around 20/mm3 or there is bleeding.

Does Trousseau syndrome depend on the tumor size?
Yes. Typically, patients with widespread metastatic malignancies develop Trousseau syndrome.

Related reading

Immune thrombocytopenia in adults: An update. CCJM, 2012.

Published: 02/11/2005
Updated: 10/02/2012

Febrile Neutropenia in a Patient on Chemotherapy

Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.

A 55-year-old CM is admitted to the hospital with a chief complaint of fever for one day.

He has a history of unresectable lung cancer (NSCLC) and has completed 6 chemotherapy courses with carboplatin and doxorubicin. During the last chemotherapy session yesterday, he was found to be febrile and was admitted to the hospital. He reports no N/V/D/C, cough, CP or abdominal pain.

He gives a history of a 10-pound weight loss over the last month and difficulty chewing because of a tender lump on the left side of the face for 2-3 weeks.

PMH

Lung cancer, diagnosed 8 months ago in stage IIIb, previous episodes of hypercalcemia, last one 20 days ago, OA.

Medications

Prevacid (lansoprazole), trazodone, Benadryl (diphenhydramine), Percocet (oxycodone and acetaminophen), tramadol, senokot, doxepin, and Perphenazine.

SH

He does not drink, has a 25 pck-yrs smoking history, no illegal drug use.

What is the most likely diagnosis?

Pneumonia?
Sepsis due to neutropenia secondary to chemotherapy?
Tooth abscess?
Meningitis?
UTI?

Physical examination

VS 39.4-20-117-126/67.
Cachectic, in no acute distress.
HEENT: Left-sided mass, 2-3 cm in size, originating from the left part of the mandible (lower jaw), tender to palpation. Supple neck, no lymphadenopathy.
Chest: decreased AE in the right lung.
CVS: Clear S1S2.
Abdomen: WNL.
Extremities: no signs of infection.

Rectal exam? The rectal examination is relatively contraindicated in patients with febrile neutropenia due to risk to introduce infection and it was not done in this patient.


The temperature chart shows fever in febrile neutropenia (click to enlarge the image).

What laboratory work would you order?

CBC+DIFF
CMP
UA
Blood Cx x 2
CXR
EKG
Jaw X-ray vs. CT scan or MRI


CBCD and CMP in febrile neutropenia (click to enlarge the images).


X-ray showed bone metastases (left). Report of the X-Ray of the mandibula report: bone metastases suspected (right) (click to enlarge the images).


CT of the chest showed air fluid level due to lung cancer. Report of the CT (right).


CXR with an air fluid level due to lung cancer. CXR report (right).

What happened?

Cultures were negative. WBC was only 1,000 with ANC of 260/mm3.

Neutropenia definition is ANC of less than 500/mm3.

What antibiotics would you start after "pan-cultures"?

Zosyn (piperacillin and tazobactam and amikacin?
Vancomycin?

Monotherapy with either imipinem or Maxipime (cefepime) is usually enough, with the addition of vancomycin because this patient with frequent hospitalizations is at risk for MRSA infection.


List of medications (click to enlarge).

What happened next?

The patient's fever resolved and he had a bone scan investigation for his neck mass. A hospice care consult was called.

Final diagnosis

Febrile neutropenia due to chemotherapy.

What did we learn from this case?

In a febrile patient undergoing chemotherapy, always consider febrile neutropenia.

Treat febrile neutropenia promptly with:
-Isolation
-"Pancultures"
-Broad spectrum antibiotics (ABx)
-Neupogen (filgrastim, G-CSF)

References

Algorithm for initial management of febrile neutropenic patients. IDSA 2002.
2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer. IDSA Guidelines, 2002.
Filgrastim in Patients with Chemotherapy-induced Febrile Neutropenia: A Double-Blind, Placebo-Controlled Trial. Darryl W. Maher et al. Ann of Int Med, 1 October 1994 | Volume 121 Issue 7 | Pages 492-501.

Publsihed: 06/12/2004
Updated: 01/07/2009

Hypercalcemia of Malignancy

55 yo AAM with PMH of inoperable NSCLC on chemotherapy was admitted to the hospital with CC: Constipation for one month and blurred vision for 1 day.

He had a abnormal lab test in the outpatient chemoTx department which was the reason for the admission.

PMH:
COPD, Smoker, Lung CA with bone mets

Meds:
MS, Oxycontin, Percocet, Tylenol, Aerosols

What is the most likely lab abnormality?
HyperCa++

What do you think is the reason for the constipation?
Opiods
HyperCa++

What should we ask to check if the chemoTx is having any effect?
Fatigue?
Appetite?
Weight loss?
He was not feeling very well in general.

What are the questions on RoS that we ask in hyperCa++?
"Stones, Bones, Moans, Psychic Groans" mnemonic
Source: FP Notebook
All were negative in this patient

What do we look for on physical exam?
VS, dehydration?
He was not orthostatic or dehydrated

Lungs: decreased air entry on R


CXR-PA view; Close-up; CXR report

What tests would you order?
CBCD, CMP

Why CBCD?
Patient is having chemoTx and may have a drop in any of the 3 blood lines, e.g. leukopenia, anemia, thrombocytopenia

Labs showed severe hypercalcemia


Labs

What would you do now?
IVF and Zometa

The so called "Lasix sandwich" (1L NS - Lasix 20 - 1L NS - Lasix 20) is not recommended anymore because most of these patients are severely dehydrated.
The goal is urine output of 150 cc/hr.

What about if the patient is having CHF? Do we need a 2D Echo?
No, negative CXR and EKG have 95% predictive value in ruling out CHF.
This patient just needs fluids: NS 500 cc bolus, and then 250 cc/hr with the goal of urine output 150-200 cc/hr.

What happened?
Patient was admitted to RMF and was treated with IVF. Zometa was not immediately available (4 mg IV infusion over 4 hours, one dose), and a Pamidronate infusion was started instead (infused over 24 hrs).


Treatment

Final diagnosis:
Hypercalcemia of malignancy

What did we learn from this case?
Hypercalcemia is a known complication of lung CA.
It is an emergency and needs treatment fast.
Hydration is the most important step, Zometa is next on the list.

Also, in this particular patient, hospice care should be recommended.

References:
A Practical Approach to Hypercalcemia - AFP 2003

Hypercalcemia due to Multiple Myeloma

Author: V. Dimov, M.D., Assistant Professor, University of Chicago
Reviewer: S. Randhawa, M.D.

A 60-year-old female presented to the ER complaining of back pain, weakness and decreased appetite for one week.

Past medical history (PMH)

Diverticulitis.

Medications

No outpatient medications.

Physical examination

VSS.
Limited movement in the lumbar spine.
No focal neurological changes.

Laboratory results

Hemoglobin 7.7 mg/dL
Hematocrit 23
Platelets of 106/mm3
BUN of 35 mg/dL
Creatinine of 2.7 mg/dL
Ca of 16.6, the repeated Ca is still 16.2.


CBC and CMP (click to enlarge the images).


Hypercalcemia (click to enlarge the images).


Urinanalysis (click to enlarge the images).

What is the most likely diagnosis?

Anemia.
Thrombocytopenia.
Renal insufficiency.
Hypercalcemia.

There is no previous baseline of laboratory results, so we cannot really say if the changes are new or chronic.

What happened?

The patient is admitted for anemia, renal insufficiency, and hypercalcemia.

What would you do next?

Correct hypercalcemia with:
NS IVI
Lasix (furosemide)
Pamidronate infusion
Calcitonin

Check:
CMP
Repeat H/H
Lumbar spine X-rays

Type and screen 2U PRBC
Transfuse 2 U PRBC if Hgb is less than 8

Work-up of anemia:
Iron profile and ferritin
B12, folate
Reticulocyte count
Peripheral smear review
Stool guaiac x 2

Protein is 13.5 mg/dL, albumin is 3.6 mg/dL.

Periphreal smear review: Normocytic anemia without polychromasia. Thrombocytopenia. Rouleax. Rule out plasma cell dyscrasia.

What is the likely diagnosis?

Multiple myeloma.

Beta 2 microglobulin is 10.6.

Immunoelectrophoresis is shown below:


Serum immunoelectrophoresis (click to enlarge the images).

What happened next?

With treatment, calcium decreased to 12.4.

A hematology consult was called. Bone marrow biopsy will be done.

Survey radiographs of the skull, spine, ribs, pelvis and upper and lower extremities (large bones):

X-ray of skull, CXR, spine (click to enlarge the images).


Pelvis X-ray, femur and fibula (click to enlarge the images).

Multiple bony structures demonstrate changes of multiple myeloma or diffuse metastatic neoplasm.

The lateral view of the calvarium demonstrates multiple focal radiolucencies. Radiographic findings would be consistent with diffuse involvement with multiple myeloma. Spinal segments demonstrate mild diffuse osteopenia. Radiographs of the upper extremity bones demonstrate radiolucencies associated with the proximal humeri bilaterally. The ribs demonstrate diffuse osteopenia with coarsening of the trabecular pattern suggesting a bone marrow replacement process. There is a pathological fracture at the lateral aspect of the left seventh rib. The AP radiograph of the pelvis demonstrates diffuse osteopenia with several focal radiolucencies involving the inferior aspects of the ilia and the inferior pubic rami and ischia bilaterally. Focal radiolucencies involving the proximal femora bilaterally suggesting a bone marrow replacement process. There is a small focal radiolucency involving the proximal right fibula which could represent early bony destructive change.

CT scans of chest, abdomen and pelvis did not show masses suggestive of malignancy. The scans did show diffuse skeletal lytic lesions which may represent multiple myeloma or other metastatic disease.

Final diagnosis

Multiple myeloma pending the bone marrow biopsy result.

Related resources


Multiple Myeloma - Mayo Clinic video: May 12, 2010 — In the following video, Rafael Fonseca, M.D., Director of the Cancer Center at Mayo Clinic in Arizona, provides an overview of the condition Multiple Myeloma (a cancer that arises from the blood marrow) and describes treatment options.

Related reading

Multiple Myeloma. NEJM review, 2011.

Published: 06/12/2006
Updated: 03/12/2011