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THROMBOCYTOPENIA                       See Heparin-induced Thrombocytopenia 2006

A. Production defect
1. Reduced thrombopoiesis megakaryocytes

• a. Marrow injury: drugs, chemicals, alcohol, radiation, infection
  Drugs: gold, sulfonamides, ethanol, thiazides, phenylbutazone, Septra.
• b. Marrow failure, acquired, congenital (Fanconi's synd, amegakaryocytic)
• c. Marrow invasion: Ca, leukemia, lymphoma, fibrosis
• d. Lack of marrow stimulus: thrombopoietin deficiency

2. Defective maturation (normal or increased megakaryocytes)

• a. Vit. B12, folate deficiency
• b. Hereditary: Wiskott Aldrich syndrome, May Hegglin anomaly

B. Sequestration (distribution disorder)
1. Splenomegaly

• a. Congestive Splenomegaly: Hepatic cirrhosis, CHF, Portal vein obstruction
• b. Infiltrative Splenomegaly: Gaucher's disease, etc. Lymphoma & myeloproliferative diseases
• c. Infections or inflammation: TB & other granulomatoses (sarcoidosis), Connective tissue diseases (SLE), vasculitis
• d. Hyperplastic responses: chronic hemolysis, sickle Hgb C disease, hereditary spherocytosis, autoimmune hemolytic anemia.

2. Hypothermic anesthesia

C. Accelerated destruction
1. Immunologic

• a. Autoantibody: ITP, SLE, lymphoreticular disorder, hemolytic anemia, drugs
  Drugs: quinidine, quinine, thiazide, diuretics, aminosalicylic, acid, acetaminophe, diazepam, sulfisoxazole, phenyltoin, heparin.
• b. Alloantibody: post transfusion purpura, fetal meternal incompatibility

2. Non immunologic

• a. Injury due to infection or prosthetic heart valve
• b. Consumption: DIC (See DIC record), ?Gram-negative septicemia.
• c. TTP (see record), preeclampsia, vasculitis; microangiopathic hemolytic anemia (MAHA), severe vascular injury, hemolyti-uremic synd.
• d. Giant hemangiomas.

D. Loss by hemorrhage & massive transfusion

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Causes of Thrombocytopenia

1. Drugs: chemotherapy, heparin, chloramphenicol, Ticlopidine, Clozepine, H2-blockers
2. Autoimmune :  a. Previously called idiopathic    b. May follow viral infection
3. Splenomegaly: liver failure, malignancy, infection
4. Viral: follows infection. ? Autoimmune. Associated with CMV, HIV
5. Isoimmune: in neonates, mother makes anti-platelet antibody
6. Neoplastic: infiltration of bone marrow prevents platelet development
7. Aplastic Anemia: pancytopenia; viral, idiopathic, autoimmune, chloramphenicol
8. Thrombotic thrombocytopenic purpura (TTP): with hemolysis, fever, mental status changes
9. Disseminated intravascular coagulopathy (DIC): consumptive coagulopathy
10. HIV Related
11. HELLP Syndrome: Follows pregnancy. Low platelets
12. Hereditary Disorders

What is the best way to determine if thrombocytopenia in a patient on multiple medications is drug-induced?
CCJM  March 2002

Approach to suspected drug-induced thrombocytopenia:
Annals IM 1998:129:886 George JN; Ann ls IM 2001; 134:346 Rizvi MA

1. Stop all drugs for which there is no clear or present indication; postulate drug most likely causing thrombocytopenia
2. stop drug most likely causing thrombocytopeniaand substitute a chemically unrelated compound for its indication
3. Observe for improvement; if improvement does not occur promptly, choose next most likely drug, substitute for it as above, and repeat cycle until thrombocytopenia resolves.

Common noncytotoxic drugs with definite or probable evidece for causing thrombocytopenia:
Annals IM 2001;134:346  Rizvi MA, George JN;   Annals IM 1998:129:886 George JN

Anti-inflammatory, analgesics

• Definite evidence: acetaminophen, diclonfenac, tolmetin
• Probable evidence: gold, ibuprofen, sulindac

Antimicrobials

• Definite evidence: amphotericin B, cephalothin, ethambutol, indinavir, levamisole, methicillin, piperacillin, quinine, refampin, sulfisoxazole, trimethoprim-sulfamethoxazole, vancomycin
• Probable evidence: ampicillin, fluconazole, oxytetracycline

Cardiovascular drugs

• Definite evidence: amiodarone, diazoxide, digoxin, qjinidine, methyldopa, minoxidil, nitroglycerine
• Probable evidence: captopril, procainamide

Central nervous system drugs

• Definite evidence:  chlorpromazine, diazepam, haloperidol, lithium
• Probable evidence: carbamazepine, phenytoin

Endocrine drugs

• Definite evidence:  aminoglutethimide, danazol, diethylstillbestrol
• Probable evidence:  chlorpropamide, glyburide

Gastrointestinal drugs

• Definite evidence:  cimetidine, mesalamine, sulfasalazine
• Probable evidence:  ranitidine

Renal drugs

• Definite evidence:  chlorothiazide
• Probable evidence:  hydrochlorothiazide

Other drugs

• Definite evidence:  atorvastatin, diatrizoate meglumine, interferon alfa, iopanoic acid, pentoxifylline, tamoxifen
• Probable evidence:  ticlopidine

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2007

For low platelets, how low is dangerous?
The answer depends on the cause of the thrombocytopenia and on whether surgery or childbirth is planned.
J.N. GEORGE -  Cleveland Clnic J ofo Med  Vol 71. April 2004  p. 277