Thrombocytopenia in the ICU

Reference: Am J Respir Crit Care Med 2000; 162:347-51

Bleeding risks:

1. Platelets above 100,000 - no abnormal bleeding, even with major surgical procedures

2. Platelets 50,000 - 100,000 - increased risk of bleeding with major trauma

3. Platelets 20,000 - 50,000 - increased risk of bleeding with minor trauma or surgical procedures

4. Platelets 10,000 - 20,000 - increased risk of spontaneous bleeding, particularly in patients with fever or infection

5. Platelets below 10,000 - high risk of spontaneous bleeding

Mechanisms:

1. Decreased platelet production:

a) chronic liver disease - results in decreased levels of hepatic thrombopietin

b) drugs: thiazides, alcohol, estrogens can cause isolated megakaryocyte hypoplasia

c) vitamin deficiency - B12 and folate

d) replacement of bone marrow - leukemia, metastatic malignancy, myelofibrosis

2. Increased platelet destruction:

a) Disseminated intravascular coagulation:

1) mechanism: release of tissue factor from endothelial cells in response to endotoxin and/or cytokines. Tissue factor in turn generates thrombin which triggers intravascular coagulation from fibrin production and consumption of coagulation factors

2) causes: sepsis, trauma, extensive surgery, cancer, obstetric complications

3) diagnosis: increased fibrinogen degredation products, low fibrinogen, thrombocytopenia, increased INR

4) treatment: treat the underlying cause; anti-thrombin III may be useful in patients with DIC due to septic shock; all-trans-retinoic acid is useful in DIC due to acute promyelocytic leukemia

b) Heparin-induced thrombocytopenia

1) non-immune (type I): platelet counts remain greater than 100,000 and fall on days 1-4 of heparin therapy; assymptomatic; no intervention necessary

2) immune (type II): platelets counts generally fall below 100,000 and thrombocytopenia occurs after day 5 of heparin therapy; high risk of thrombosis; immediate discontinuation when HIT suspected is required; treat with lepirudin until platelet count rises above 100,000 then start coumadin

c) Thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (HUS/TTP)

1) mechanism: abnormal formation of platelet aggregates possibly caused by deficiency of von Willibrand factor cleaving protease

2) causes: often idiopathic but may be assocaited with E. coli O157:H7, mucinous adenocarcinomas, drugs (estrogens, mitomycin, cisplatin, cyclosporin, tacrolimus, OKT3, quinine, ticlopidine)

3) diagnosis: classic pentad (not all must be present):

- neurologic symptoms

- microangiopathic hemolytic anemia

- thrombocytopenia

- renal disease

- fever

4) treatment: plasma exchange

d) Drugs:

Quinidine	Heparin	Acetaminophen
Quinine	Digoxin	Phenylbutazone
Ampicillin	Aspirin	p-Aminosalicylate
Penicillin	Valproic acid	Rifampin
Thiazides	Ranitidine	Acetazolamide
Furosemide	Cimetidine	Anazolene
Chlorthalidone	Danazol	Arsenic
Phenytoin	Procainamide
Alphamethyldopa	Carbamazepine

e) Idiopathic thrombocytopenic purpura (ITP)

1) mechanism: development of autoantibodies to platelets

2) causes: usually unknown or following a viral infection. 90% of adults are younger than 40 yrs and there is a 4:1 female predominance

3) diagnosis:

- physical exam: normal spleen, petechiae, ecchymosis

- antiplatelet antibodies: can be non-specific; false positive results can occur with non-specifically adsorbed IgG on platelet surfaces

- bone marrow aspirate/biopsy: normal megakaryocytes

4) treatment:

- prednisone (1 - 2 mg/kg/day)

- intravenous immunoglobulin (1 gm/kg/day x 2 days)

- splenectomy

- others: danazol, vincristine, cyclophosphamide, azothioprine

f) Lymphoproliferative disorders - antibody mediated platelet destruction

g) Systemic lupus erythematosus - antibody mediated platelet destruction

h) Viral illness - antibody mediated platelet destruction

1) HIV

2) CMV

3) mononucleosis

i) Sepsis

j) Pre-eclampsia: 15% of patients develop thrombocytopenia

k) HELLP syndrome (Hemolysis with microangiopathic blood smear, Elevated Liver enzymes, and Low Platelets in pregnancy): can occur as a subset of pre-eclampsia or as an independent entity. Treatment is steroids and if patients fail to improve within 3 days of steroids, treatment is plasma exchange

3. Dilutional thrombocytopenia:

a) occurs during massive transfusion for hemorrhage (eg, greater than 15-20 units of PRBCs.

4. Distributional thrombocytopenia:

a) splenic sequestration

5. Spurious thrombocytopenia:

a) occurs from insufficient anticoagulation of collected blood or from EDTA-dependent agglutinins

Evaluation:

1. Physical examination:

splenic enlargement - sequestration

2. Peripheral blood smear:

vacuolated neutrophils - sepsis

schistocytes

- small numbers: DIC

- large numbers: TTP

3. Laboratory testing:

elevated LDH - TTP

increased D-dimer, decreased fibrinogen, increased PT & PTT - DIC

abnormal heparin-induced thrombocytopenia studies - HIT

4. Bone marrow aspirate/biopsy:

hypocellular - aplastic anemia

increased/normal megakaryocytes - peripheral platelet destruction/sequestration

megaloblastic - B12, folate deficiency

decreased megakaryocytes - isolated megakaryocyte hypoplasia, bone marrow replacement

Updated August 27, 2000

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