Thrombocytopenia, ITP, HIT & TMA

Frame the platelet count

Mild 100–150k, moderate 50–99k, severe <50k (Hematology 2012;2012:191; ). Bleeding risk is not linear: <50k with surgery or active bleeding, <30k with mild trauma, <10k spontaneous. a new thrombocytopenia with a citrated platelet count — EDTA clumping is an embarrassing consult.

↓ Production

Infection: sepsis, HIV/HCV, VZV/CMV/EBV, parvo, tickborne
Nutrition: alcohol, ↓ B12, ↓ folate
Drugs: antibiotics, chemo (ASH Edu 2018;2018:576)
Neoplasm: MDS, marrow infiltration, primary heme malignancy
Hereditary, cirrhosis, aplastic anemia, some von Willebrand disease

↑ Destruction

Immune: ITP, SLE/APS, RA, lymphoma, post-transfusion purpura
Drugs: heparin, MTX, antibiotics, AEDs, GPIIb/IIIa inhibitors, quinine
MAHA: DIC, TTP, HUS, malignant hypertension, preeclampsia/HELLP
Mechanical: CVVH, bypass, ECMO, IABP, valves

Sequestration / dilution: hypersplenism, hemangioma, massive transfusion, hypothermia, gestational thrombocytopenia.
History: GI, GU, epistaxis, headache, mucocutaneous bleeding, timing of the drop. New headache → consider head CT.
Rule out the alarms first: HIT, TMA, catastrophic APS. Then the common: infection, drug, immune, nutrition, spleen, MDS.

Labs that match the story

All
First draw
CBC, BMP, LFTs, coags, special slide, type and screen, HIV, HCV, pregnancy test, citrated platelet count.
Mild
Asymptomatic 100–150k
Alcohol and other risk factors, exam, other cytopenias, smear, HIV/HCV, B12, folate. This is a common cause of over-testing — do not send a TMA panel on a 142k platelet count and a normal smear.
MAHA
Schistocytes on the slide
LDH, haptoglobin, DAT, retics, D-dimer, fibrinogen.
APS
SLE / APS in the differential
ANA, lupus anticoagulant, anti-cardiolipin, anti-β2GP1.

Concern for marrow disease: hematology consult ± biopsy.

ITP

Immune thrombocytopenia is anti-platelet antibody clearing platelets and binding megakaryocytes, so production is only near-normal (; ; -3582). Primary (~80%) has no associated disease. Secondary rides along with SLE, APS, CVID, CLL, Evans syndrome, HCV, HIV, and drugs.

Presentation: a precipitous drop. Asymptomatic or mucocutaneous bleeding. About 10% have AIHA (Evans).
Thrombopoietin level may predict response to TPO-receptor agonists ().
Prognosis: <10% resolve spontaneously; up to 50% respond to first-line therapy; ~70% become chronic. ICH ~1.4%; severe bleeding ~9.5%.
Diagnosis of exclusion: platelets <100k and nothing else explains it. 'Response' means platelets double to ≥30k within 3 months.

Treat the count and the bleed, not the label

≥30k
Observe if asymptomatic / minor bleed
Consider steroids if elderly, comorbid, on anticoagulation or antiplatelets, upcoming procedures, or the count is hugging 30k.
10–29k
Steroids ± IVIG
RhoGAM if RhD-positive. If not bleeding, do not give platelets — they are destroyed and the count can fall further ().
<10k
Steroids plus IVIG
Consider romiplostim (TPO-RA). Still no platelets unless you are worried about bleeding.
Bleed
Life-threatening or wet purpura
Platelets, IVIG, pulse steroids (methylprednisolone and dexamethasone), aminocaproic acid or TXA, romiplostim, rituximab.

Refractory/recurrent: increase romiplostim, add rituximab.
Last resort after >12 months: splenectomy (>50% effective) or fostamatinib (a splenic TKI).

HIT

Heparin-induced thrombocytopenia type 2 is IgG against PF4–heparin complexes that activate platelets into a hypercoagulable state (; ; ). Any heparin counts — UFH, LMWH, even flushes.

HIT type 1

Mild drop, nadir not below 100k
Day 1–2 of heparin
Not immune, not clinically significant
Continue heparin

HIT type 2

Day 5–10 (or <24 h if heparin in the last 100 days)
Platelet fall >50%, nadir typically 40–80k
Thrombosis in 30–50%: skin necrosis, DVT/PE, arterial; GIB ~3%
Delayed-onset HIT can present up to 3 weeks after the last dose

0–3: HIT unlikely (NPV ~99%). ≥4: treat as HIT while assays run. If information is incomplete, score high and recalculate.

4Ts	2 points	1 point	0 points
Thrombocytopenia	>50% fall and nadir ≥20k	30–50% fall or nadir 10–19k	<30% fall or nadir <10k
Timing	Clear day 5–10, or ≤1 day with heparin in the last 30 days	Probable 5–10, ≤1 day with heparin 31–100 days, or >10 days	≤4 days without recent heparin
Thrombosis	New thrombosis, skin necrosis, or systemic reaction after a bolus	Progressive/recurrent/silent thrombosis, or erythematous skin lesions	None
oTher cause	None apparent	Possible	Definite

Score ≥4 — do not wait for the lab

1
Stop and swap
Stop all heparin. Reverse warfarin (to prevent venous limb gangrene/skin necrosis). Start a non-heparin anticoagulant. No platelet transfusion unless severe hemorrhage.
2
Send assays
Anti-PF4 ELISA, then serotonin-release assay (functional gold standard). PF4 negative: HIT unlikely, heparin may resume. PF4 OD ≥2, or OD ≥1.5 with 4Ts ≥6: HIT likely. Otherwise wait for the SRA.
3
Look for clot
Upper- and lower-extremity ultrasound. Isolated HIT still needs anticoagulation until the count recovers.

Agent	Use when	Caveat
Argatroban (IV)	Renal failure and surgical patients (short half-life)	Hepatic clearance. Raises INR. Monitor with chromogenic factor Xa 20–40% when overlapping to warfarin
Bivalirudin (IV)	HIT undergoing PCI; preferred in liver failure	Labeled for PCI
Fondaparinux (SQ)	Stable, non-surgical, average bleed risk	Contraindicated if CrCl <30; irreversible
DOAC	Average bleed risk, once stable	Do not start warfarin until platelets >150k for 2 consecutive days

Duration: no thrombosis — until platelets >150k, at least 4 weeks. With thrombosis — at least 3 months.
Add heparin to the allergy list. For future VTE prophylaxis, pick something else.
If a strong indication returns (bypass) and HIT was >100 days ago with a now-negative anti-PF4, small series suggest re-exposure is possible (; ).
The count typically recovers in ~7 days.

Thrombotic microangiopathy

Microthrombi produce MAHA (↓ Hb, ↑ LDH, ↓ haptoglobin, schistocytes, DAT-negative), consume platelets, and infarct end organs (). Name the syndrome, then the drug list.

DITMA drugs: gemcitabine, oxaliplatin, quetiapine, quinine, tacrolimus, cyclosporine, bevacizumab, opioids. Stop the drug.
Secondary TMA: DIC, infection, malignancy, SLE/APS, scleroderma, malignant hypertension, HELLP, post-HSCT.

TTP (platelets often <30k)

ADAMTS13 deficient (inherited or acquired) → ultra-large vWF multimers → platelet microthrombi
Purpura, GI symptoms, fluctuating neurology, fever, mild–moderate AKI
PLASMIC score intermediate/high; send ADAMTS13 activity before PLEX if you can, but do not delay PLEX
Plasma exchange, steroids, rituximab. Caplacizumab in selected protocols
Do not transfuse platelets to 'correct' the count unless severe bleed. Transfusion is not clearly tied to higher mortality or CNS events (;873), but it is not the therapy

HUS (platelets often >30k)

ST-HUS (Shiga toxin, O157:H7 E. coli, Shigella): bloody diarrhea, severe AKI, neuro symptoms rare. Stool for organism or toxin. Supportive care (IVF, dialysis). Avoid antibiotics for STEC — they may increase toxin release ()
Complement-mediated (atypical HUS): severe AKI ± extra-renal disease (CNS, cardiac, pulmonary hemorrhage, pancreatitis) in ~20%
aHUS: complement genotyping, anti-complement antibody. Plasma exchange while TTP is excluded, then eculizumab (). Vaccinate for meningococcus

Tonight, before ADAMTS13 returns

1
Smear and consult
Schistocytes plus thrombocytopenia is a hematology page. Monitor urine output.
2
Start PLEX
Therapeutic plasma exchange is first-line while TTP is on the table. Transfuse RBCs for symptomatic anemia.
3
Platelets only if needed
Typical TMA practice: platelets for <20k, or <50k with bleeding or a procedure — and still avoid reflexive correction in TTP.
4
Complement labs
C3/C4. Stop DITMA drugs. Eculizumab is for aHUS after TTP is excluded, not a TTP substitute.