Thrombocytopenia

Jamila Mammadova

Background 

  • Classified as either mild (100K-149K), moderate (50K-99K), or severe (<50K or <30K)
  • Can be a component of pancytopenia or bicytopenia
  • Pseudothrombocytopenia: EDTA-dependent platelet clumping (lab artifact)

Mechanism

Causes

Example(s)
Decreased platelet production / bone marrow suppression Drug induced (most common) Antibiotics (vancomycin, linezolid, bactrim), antivirals (val/gancyclovir, zidovudine), immunosuppressants (AZA, MMF, tacrolimus), antiepileptics (valproate, carbamazepine, phenytoin), antithyroid (PTU, methimazole), NSAIDs, chemotherapies, allopurinol, colchicine
Decreased TPO production Liver disease, medications, EtOH, nutritional deficiencies
Infection Sepsis, HIV, tick-borne i.e. RMSF, anaplasma, erhlichia, leptospirosis, parvovirus, TB, NTM, fungal
Primary hematologic syndromes and malignancies Myelodysplastic syndrome, heme malignancies, PNH
Nutritional deficiency Vitamin B12, folate, copper (primary vs secondary to zinc toxicity)
Infiltrative Malignancies (leukemia, lymphoma, myeloma, metastatic solid tumors), amyloidosis, fibrosis (myelofibrosis)
Toxicity Radiation, EtOH, heavy metals
Redistribution Splenomegaly Conditions that cause an increase in spleen size (lymphoproliferative disorders) and conditions that cause spleen congestion (portal HTN)
Inherited Genetics Gray platelet syndrome, congenital amegakaryocytic thrombocytopenia, Wiskott-Aldrich syndrome
Increased destruction Immune mediated Immune thrombocytopenic purpura (ITP), druginduced thrombocytopenia (quinine, rifampin, sulfonamides, beta-lactams, vancomycin, meropenem, valacyclovir, PPIs, H2 blockers, anti MTB therapy), post-transfusion purpura (PTP), heparin induced thrombocytopenia (HIT)
Autoimmune diseases SLE, APS, hypo- and hyperthyroid
Infections Sepsis (especially GN bacteremia), HIV, HBV, HCV, CMV, EBV, dengue, malaria, H. pylori
Increased consumption TTP (congenital and acquired), HUS (Shiga toxin or atypical-HUS i.e. complement-mediated) Immune thrombocytopenic purpura (ITP), druginduced thrombocytopenia (quinine, rifampin, sulfonamides, beta-lactams, vancomycin, meropenem, valacyclovir, PPIs, H2 blockers, anti MTB therapy), post-transfusion purpura (PTP), heparin induced thrombocytopenia (HIT)
Secondary thrombotic microangiopathies (TMA) DIC (sepsis, trauma, APML, pancreatitis, transfusion reaction), HELLP syndrome, malignant HTN, scleroderma renal crisis, drug-induced (calcineurin inhibitors, chemo, quinines, cocaine), catastrophic APLS, GvHD, TBI, infection-associated (strep pneumo, HIV)
Massive hemorrhage Trauma, postpartum, coagulopathy
Others Dilutional Massive transfusion without platelet replacement
Mechanical destruction Prosthetic heart valves, cardiopulmonary bypass

Presentation

  • Usually asymptomatic
  • The rate of platelet count drop is more clinically significant than absolute platelet count
  • Bleeding due to low platelet counts presents as non-blanching rash (petechiae and purpura), bruising, gingival and nosebleed, menorrhagia
  • Severe bleeding may occur, typically with platelet count <10K, and can present with hematuria, melena, hematochezia, intracranial hemorrhage (especially if prior CNS malignancy, life-threatening)
  • Some causes of thrombocytopenia have a paradoxically increased risk of thrombosis (HIT, DIC, TMA)

Evaluation

  • Repeat CBC w/ diff
  • Peripheral smear or citrated platelet count (to rule out pseudothrombocytopenia) PLUS immature platelet fraction (IPF)
    • Low IPF can point toward decreased platelet production vs. high IPF is expected in compensation for platelet destruction/consumption
  • Medication review to look for any offending drugs (see table above)
  • TMA/DIC labs: haptoglobin, LDH, LFTs, PT/PTT, fibrinogen, D-dimer, peripheral smear (for schistocytes), retics (will be high), renal function.. Can use ISTH DIC score to assess likelihood of DIC.
  • Infectious work-up (as clinically indicated):
    • Viral serologies: HIV, HBV, HCV, EBV, CMV, parvovirus
    • Sepsis: blood cultures, urine culture, sputum cultures
    • Fungal work-up: 1,3-Beta-D-Glucan, aspergillus galactomannan, urine blasto Ag, urine and serum histo Ag, crypto Ag
    • Tick-borne: RMSF, Ehrlichia, Anaplasma
    • Leptospirosis
    • TB and/or NTM: AFB, interferon-Gamma release assay
  • Autoimmune work-up (as clinically indicated): ESR, CRP, ANA w/ reflex, RF, APL antibodies
  • HIT work-up: Calculate 4T score: if ≥4, order HIT Ab ELISA. If (+) or equivocal, get serotonin-release assay (SRA) with reflex
  • Nutritional studies: B12, folate, copper, zinc
  • TSH to screen for thyroid disease
  • Abdominal U/S to look for splenomegaly (or review recent imaging)
  • Bone marrow biopsy: co-existing cytopenias (especially if not new), blasts on smear, or concerning flow cytometry findings
  • If pregnant: HELLP panel (haptoglobin, LDH, LFTs, BMP, urine PCr)

Management

  • Hold DVT prophylaxis for platelet ≤50K
  • Hold anti-platelets (NSAIDs, ASA)
  • Three thrombocytopenia syndromes that are immediately life-threatening: DIC, HIT, and HUS – can’t miss
  • If concern for bleeding, get type and screen and blood consent
  • Platelet transfusion goals and indications
    • Generally, not indicated if not bleeding and platelet >10K
    • Avoid transfusions in HIT, TTP, HUS
    • One unit of platelet is expected to increase levels by 10-40K, but it depends on weight, ongoing rate of consumption, destruction, distribution
    • CNS or ocular bleeding, NSGY, plan for ocular surgery: goal >100K
    • Pt actively bleeding, most surgeries, therapeutic endoscopy: goal > 50K
    • Plan for central line, bronch, LP, diagnostic endoscopy, or bone marrow biopsy: goal >20K
    • Afebrile, hospitalized pts for bleeding prophylaxis: goal >10K
  • HIT management: Stop any heparin product and start argatroban. NO platelet transfusions.
  • ITP is a diagnosis of exclusion. Consult heme for management.
  • Schistocytes on smear:
    • Think TTP, HUS, or DIC when there are schistocytes on smear and thrombocytopenia
    • For TTP: calculate PLASMIC score and consider ordering ADAMTS13 levels. Consult hematology about PLEX asap. Vascath is needed for PLEX.
    • If DIC: consult hematology for management (supportive transfusions and may require heparin), identify underlying cause.
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