thrombocytopenia
transfuse goals
10k, 20k, 50k, 100k
regular, fever, surgery, nsgy
Definitions: 100-150k mild, 50-99k mod, <50k severe. Bleed risk: <50k w/ surgery/active bleed, <30k w/ mild trauma, <10k spontaneous
Production:
Infection: sepsis, HIV/HCV, VZV/CMV/EBV, parvo, tickborne
Nutrition: EtOH, B12, folate
Drugs: abx, chemo, ASHEdu 2018;2018:576
Neoplasm: MDS, BM infiltration, 1° heme
Other: cirrhosis (TPO), aplastic anemia, some vWD
Destruction:
Immune: ITP, SLE/APLS, RA, lymphoma, posttransfusion
Drugs: heparin, MTX, abx, anti-GPIIb/IIIa, quinine, NEJM2007;357:580
MAHA: DIC, TTP, HUS, mHTN, preeclampsia/HELLP
Shearing: CVVH, bypass, IABP, vasculitis, hemangioma (Kasabach-Merritt)
Sequestration/Dilution:
Hypersplenism (cirrhosis, portal HTN)
Massive transfusion
Hypothermia
Workup:
• H&P focused on bleeding (GI, GU, epistaxis, HA, mucocutaneous), etiology, timing of plt . If new HA: consider CTH
• R/o alarming causes: HIT, TMA, catastrophic APLS. Identify common causes: infxn, drug, immune, nutrition, hypersplenism, MDS
• Initial labs: CBC/d, BMP, LFTs, coags, special slide, T+S, HIV, HCV, pregnancy test, citrated plt count (r/o pseudo-thrombocytopenia)
• If c/f MAHA (e.g. schistocytes on slide): add LDH, haptoglobin, DAT, retics, D-dimer, fibrinogen, fractionated bilirubin
• If c/f SLE/APLS: add ANA, lupus anticoagulant, anti-cardiolipin, anti-β2GP1
• If c/f BM disease: consider BM biopsy (rarely done)
ITP:
AutoAbs against plts and megakaryocytes. Defined by isolated plt <100k, dx of exclusion (anti-plt Ab not useful)
Presentation: asx or mucocutaneous bleeding; 10% of ITP has AIHA = Evan’s syndrome. Screen for H. pylori (tx may plts in ITP)
Prognosis: <10% spontaneous resolution, up to 50% recover with 1st line tx. 1.4% risk of ICH, 9.5% risk of severe bleeding
Management: “response” = plt increase 2X to ≥30k within 3mo
• Plt ≥30k & asx/minor bleed: observe; consider steroids if elderly, comorbidities, on AC/anti-plts, upcoming procedures, & plt near 30k
• Plt 10k-29k: steroids ± IVIG; if not bleeding, do not give plts (will be destroyed)
o steroids (takes 4-14d to work): dexamethasone 40mg/d x4d, methylpred 1g/d x3d, or prednisone 60mg/d x3w w/ taper
o IVIG (takes 2-4d to work, lasts 2-3w): 1g/kg/d x2d
• Plt <10k: steroids + IVIG, consider romiplostim, do not give plts unless c/f bleeding
o romiplostim (takes 5-14d to work): 3-5mcg/kg SQ and repeat weekly until response
• Severe bleeding: plt transfusions, IVIG, steroids, Amicar (0.1g/kg/30min gtt 0.5-1g/h)/TXA, romiplostim
• Refractory/recurrent: romiplostim at increasing doses, rituximab, fostamatinib; last resort = splenectomy (itself only 50% effective)
HEPARIN - I NDUCED T HROMBOCYTOPENIA (HIT) (Blood Adv 2018;2:3360; Blood 2017;129:2864; NEJM 2015;373:252)
IgG anti-PF4-heparin complex binds & activates plts, hypercoagulable state. Can occur with any heparin (UFH, LMWH, heparin flushes)
Presentation: 5-10d after exposure, decrease plt >50%, nadir 40-80k, thrombosis in 30-50% (skin necrosis, DVT/PE, arterial)
• Consider rapid-onset HIT if <24h with prior exposure within 100d; delayed-onset can present up to 3w after last heparin
Diagnosis/Management: 4Ts greater than 4
• Calculate 4Ts Score. If 0-3: HIT unlikely (NPV 99%), OK to continue heparin. If ≥4:
1) Stop heparin, reverse warfarin (prevent skin necrosis), and start non-heparin AC. No plt transfusion unless severe hemorrhage
2) Send anti-PF4. Send serotonin release assay (SRA) (gold standard, long to result). Do not wait for results to do Step 1
o PF4 neg: HIT unlikely; OK to resume heparin. PF4 OD ≥2, or OD ≥1.5 with 4Ts ≥6: HIT likely. Otherwise: decide based on SRA
• Duration of AC: if no thrombosis, until plt >150k; if thrombosis, typically 3-6mo. AC options:
o Fondaparinux (IV or SQ): for stable non-surgical patients, contraindicated if GFR <30, irreversible
o Argatroban (IV): preferred in renal failure & surgical pts, monitor w/ chromogenic Xa (goal 20-40%)
o Bivalirudin (IV): only approved for HIT undergoing PCI, preferred in liver failure
o DOACs for non-urgent AC: apixaban, edoxaban, rivaroxaban, dabigatran
o Warfarin: not until plt >150K for 2 consecutive days
• Add heparin to allergies. Avoid future heparin (use alt. AC for VTE ppx), though if compelling indication (e.g., bypass) small studies
suggest no increased risk of HIT in pts with h/o HIT >100d prior if anti-PF4 now neg (NEJM 2001;344:1286; NEJM 2000;343:515)
4T score
Thrombocytopenia Platelet count fall >50% AND platelet nadir ≥20+2 Platelet count fall 30–50% OR platelet nadir 10–19+1 Platelet count fall <30% OR platelet nadir <100 Timing of platelet count fall Clear onset between days 5–10 OR platelet fall ≤1 day (prior heparin exposure within 30 days)+2 Consistent with days 5–10 fall, but not clear; onset after day 10 OR fall ≤1 day (prior heparin exposure 30–100 days ago)+1 Platelet count fall <4 days without recent exposure0
10k, 20k, 50k, 100k
regular, fever, surgery, nsgy
Definitions: 100-150k mild, 50-99k mod, <50k severe. Bleed risk: <50k w/ surgery/active bleed, <30k w/ mild trauma, <10k spontaneous
Production:
Infection: sepsis, HIV/HCV, VZV/CMV/EBV, parvo, tickborne
Nutrition: EtOH, B12, folate
Drugs: abx, chemo, ASHEdu 2018;2018:576
Neoplasm: MDS, BM infiltration, 1° heme
Other: cirrhosis (TPO), aplastic anemia, some vWD
Destruction:
Immune: ITP, SLE/APLS, RA, lymphoma, posttransfusion
Drugs: heparin, MTX, abx, anti-GPIIb/IIIa, quinine, NEJM2007;357:580
MAHA: DIC, TTP, HUS, mHTN, preeclampsia/HELLP
Shearing: CVVH, bypass, IABP, vasculitis, hemangioma (Kasabach-Merritt)
Sequestration/Dilution:
Hypersplenism (cirrhosis, portal HTN)
Massive transfusion
Hypothermia
Workup:
• H&P focused on bleeding (GI, GU, epistaxis, HA, mucocutaneous), etiology, timing of plt . If new HA: consider CTH
• R/o alarming causes: HIT, TMA, catastrophic APLS. Identify common causes: infxn, drug, immune, nutrition, hypersplenism, MDS
• Initial labs: CBC/d, BMP, LFTs, coags, special slide, T+S, HIV, HCV, pregnancy test, citrated plt count (r/o pseudo-thrombocytopenia)
• If c/f MAHA (e.g. schistocytes on slide): add LDH, haptoglobin, DAT, retics, D-dimer, fibrinogen, fractionated bilirubin
• If c/f SLE/APLS: add ANA, lupus anticoagulant, anti-cardiolipin, anti-β2GP1
• If c/f BM disease: consider BM biopsy (rarely done)
ITP:
AutoAbs against plts and megakaryocytes. Defined by isolated plt <100k, dx of exclusion (anti-plt Ab not useful)
Presentation: asx or mucocutaneous bleeding; 10% of ITP has AIHA = Evan’s syndrome. Screen for H. pylori (tx may plts in ITP)
Prognosis: <10% spontaneous resolution, up to 50% recover with 1st line tx. 1.4% risk of ICH, 9.5% risk of severe bleeding
Management: “response” = plt increase 2X to ≥30k within 3mo
• Plt ≥30k & asx/minor bleed: observe; consider steroids if elderly, comorbidities, on AC/anti-plts, upcoming procedures, & plt near 30k
• Plt 10k-29k: steroids ± IVIG; if not bleeding, do not give plts (will be destroyed)
o steroids (takes 4-14d to work): dexamethasone 40mg/d x4d, methylpred 1g/d x3d, or prednisone 60mg/d x3w w/ taper
o IVIG (takes 2-4d to work, lasts 2-3w): 1g/kg/d x2d
• Plt <10k: steroids + IVIG, consider romiplostim, do not give plts unless c/f bleeding
o romiplostim (takes 5-14d to work): 3-5mcg/kg SQ and repeat weekly until response
• Severe bleeding: plt transfusions, IVIG, steroids, Amicar (0.1g/kg/30min gtt 0.5-1g/h)/TXA, romiplostim
• Refractory/recurrent: romiplostim at increasing doses, rituximab, fostamatinib; last resort = splenectomy (itself only 50% effective)
HEPARIN - I NDUCED T HROMBOCYTOPENIA (HIT) (Blood Adv 2018;2:3360; Blood 2017;129:2864; NEJM 2015;373:252)
IgG anti-PF4-heparin complex binds & activates plts, hypercoagulable state. Can occur with any heparin (UFH, LMWH, heparin flushes)
Presentation: 5-10d after exposure, decrease plt >50%, nadir 40-80k, thrombosis in 30-50% (skin necrosis, DVT/PE, arterial)
• Consider rapid-onset HIT if <24h with prior exposure within 100d; delayed-onset can present up to 3w after last heparin
Diagnosis/Management: 4Ts greater than 4
• Calculate 4Ts Score. If 0-3: HIT unlikely (NPV 99%), OK to continue heparin. If ≥4:
1) Stop heparin, reverse warfarin (prevent skin necrosis), and start non-heparin AC. No plt transfusion unless severe hemorrhage
2) Send anti-PF4. Send serotonin release assay (SRA) (gold standard, long to result). Do not wait for results to do Step 1
o PF4 neg: HIT unlikely; OK to resume heparin. PF4 OD ≥2, or OD ≥1.5 with 4Ts ≥6: HIT likely. Otherwise: decide based on SRA
• Duration of AC: if no thrombosis, until plt >150k; if thrombosis, typically 3-6mo. AC options:
o Fondaparinux (IV or SQ): for stable non-surgical patients, contraindicated if GFR <30, irreversible
o Argatroban (IV): preferred in renal failure & surgical pts, monitor w/ chromogenic Xa (goal 20-40%)
o Bivalirudin (IV): only approved for HIT undergoing PCI, preferred in liver failure
o DOACs for non-urgent AC: apixaban, edoxaban, rivaroxaban, dabigatran
o Warfarin: not until plt >150K for 2 consecutive days
• Add heparin to allergies. Avoid future heparin (use alt. AC for VTE ppx), though if compelling indication (e.g., bypass) small studies
suggest no increased risk of HIT in pts with h/o HIT >100d prior if anti-PF4 now neg (NEJM 2001;344:1286; NEJM 2000;343:515)
4T score
Thrombocytopenia Platelet count fall >50% AND platelet nadir ≥20+2 Platelet count fall 30–50% OR platelet nadir 10–19+1 Platelet count fall <30% OR platelet nadir <100 Timing of platelet count fall Clear onset between days 5–10 OR platelet fall ≤1 day (prior heparin exposure within 30 days)+2 Consistent with days 5–10 fall, but not clear; onset after day 10 OR fall ≤1 day (prior heparin exposure 30–100 days ago)+1 Platelet count fall <4 days without recent exposure0
Thrombosis or other sequelae New thrombosis OR skin necrosis; acute systemic reaction post-IV heparin bolus+2 Progressive OR recurrent thrombosis; non-necrotizing skin lesions; suspected thrombosis (not proven)+1 None0
Other causes for thrombocytopenia None apparent+2 Possible+1 Definite0
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