Thrombocytopenia
Claudia Bale
Background
- Mild (100-149K), moderate (50-99K), severe (<50K); may be component of pancytopenia/bicytopenia.
- Significant plt drop (even within normal range) warrants evaluation.
| Mechanism | Causes | Example(s) |
|---|---|---|
| Decreased platelet production / bone marrow suppression | Drug induced (most common) | Antibiotics (vancomycin, linezolid, bactrim, piperacillin), antivirals (val/gancyclovir, zidovudine), immunosuppressants (AZA, MMF, tacrolimus), antiepileptics (valproate, carbamazepine, phenytoin), antithyroids (PTU, methimazole), NSAIDs, chemotherapies, allopurinol, colchicine |
| Decreased TPO production | Liver disease, medications, EtOH, nutritional deficiencies | |
| Infection | Sepsis, HIV, tick-borne (RMSF, anaplasma, ehrlichia), leptospirosis, parvovirus, TB, NTM, fungal | |
| Primary hematologic syndromes and malignancies | MDS/CCUS, heme malignancies, PNH, aplastic anemia | |
| Nutritional deficiency | B12, folate, copper (primary vs zinc toxicity) | |
| Infiltrative | Leukemia, lymphoma, myeloma, metastatic solid tumors, amyloidosis, myelofibrosis | |
| Toxicity | Radiation, EtOH, heavy metals | |
| Redistribution | Splenomegaly | Lymphoproliferative disorders, portal HTN (cirrhosis, MASLD) |
| Inherited | Genetics | Gray platelet syndrome, congenital amegakaryocytic thrombocytopenia, Wiskott-Aldrich, Bernard-Soulier (often misdiagnosed as ITP) |
| Increased destruction | Immune mediated | ITP, drug-induced (quinine, rifampin, sulfonamides, beta-lactams, vancomycin, PPIs, H2 blockers, anti-MTB therapy), ICIs (pembrolizumab, nivolumab, ipilimumab), PTP, HIT, PITT/VITT |
| Autoimmune diseases | SLE, APS, hypo- and hyperthyroid, Evans syndrome | |
| Infections | Sepsis (especially GN bacteremia), HIV, HBV, HCV, CMV, EBV, dengue, malaria, H. pylori | |
| Increased consumption | Primary thrombotic microangiopathies (TMA) | TTP (congenital/acquired), HUS (Shiga toxin), complement-mediated TMA (aHUS) |
| Secondary thrombotic microangiopathies (TMA) | DIC (sepsis, trauma, APML, pancreatitis, transfusion reaction), HELLP, malignant HTN, scleroderma renal crisis, drug-induced (calcineurin inhibitors, chemo, quinines, cocaine), catastrophic APLS, GvHD, TBI | |
| Massive hemorrhage | Trauma, postpartum, coagulopathy | |
| Others | Dilutional | Massive transfusion without platelet replacement |
| Mechanical destruction | prosthetic valves, CPB, ECMO, IABP |
Presentation
- Often asymptomatic; rate of drop more significant than absolute count.
- Petechiae, purpura, bruising, gingival/nosebleed, menorrhagia; wet purpura predicts serious hemorrhage.
- Severe spontaneous bleeding rare; most likely plt <20K, esp <10K: hematuria, melena, hematochezia, ICH (life-threatening).
- Some causes have paradoxical thrombosis risk: HIT, PITT/VITT, DIC, TMA, APS, PN.
Evaluation
- Repeat CBC w/ diff; smear or citrated plt count to r/o pseudo thrombocytopenia.
- IPF: low → decreased production; high → destruction/consumption.
- Med review (see table); note temporal relationship to new drugs (onset typically 1-2 weeks).
- All pts: metabolic panel, LFTs, HIV, HCV.
- Can’t-miss life threatening emergencies: DIC, HIT/PITT, TTP/HUS.
- Hemolysis/TMA/DIC labs: haptoglobin, LDH, PT/PTT, fibrinogen, LFTs, D-dimer, smear, retics, Cr.
- Schistocytes on smear: Think TTP, HUS, DITMA, DIC.
- Calculate PLASMIC score (MD CALC) for likelihood of TTP.
- If TTP likely, send ADAMTS13, also can differentiate from HUS.
- ISTH DIC score to assess likelihood of DIC.
- HIT work-up: 4T score: if ≥4, order HIT Ab ELISA. If (+) or equivocal --> serotonin-release assay (SRA) with reflex.
- Infectious work-up (if suspected): 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 (if suspected): ANA w/ reflex, RF, APL antibodies.
- Nutritional: B12, folate, copper, zinc.
- TSH.
- Abdominal U/S for splenomegaly (or review recent imaging).
- Bone marrow biopsy: if unexplained cytopenias, blasts, or concerning flow.
- f pregnant: HELLP panel (haptoglobin, LDH, LFTs, BMP, urine PCr).
Management
- Hold DVT ppx for plt ≤50K; hold antiplatelets. Plt >50K does NOT protect against thrombosis — continue ppx if indicated.
- If bleeding concern --> type & screen, consent.
- Plt Transfusion goals per 2025 AABB/ICTMG.
- CNS/ocular bleed, neurosurgery, major cardiac/ortho: goal >100K.
- Active bleeding, most surgeries, therapeutic endoscopy: goal >50K.
- Central line, bronch, LP, diagnostic endoscopy, BMBx: goal >20K.
- Afebrile, hospitalized, prophylaxis: goal >10K; not indicated if no bleeding & plt >10K.
- 1 unit raises plt ~10-40K (varies by weight, etiology, rate of consumption).
- Avoid transfusion in HIT, TTP, HUS.
- HIT: Stop ALL heparin (incl flushes, LMWH); start non-heparin anticoagulant (e.g. argatroban, fondaparinux). NO plt transfusions.
- ITP: Dx of exclusion. Consult heme. BMBx not required for all. TPO-RA + immunomodulator for refractory; newer agents (rilzabrutinib, ianalumab) available.
- TTP consult heme for PLEX urgently (Vascath needed).
- DIC: supportive transfusions ± heparin; treat underlying cause.