Thrombocytopenia: ITP/TTP/HUS/HIT/DIC

Thrombocytopenia (Dr Arora, USC Essentials)

ITP

• childhood: acute, self-limiting, 2-3 weeks post immunization or infection
• adult: insiduous, chronic, no preceding illness
• symptoms: platelet-type) bleeding (superficial, mucosal, gingival, petechiae) vs deep bleed/coagulopathy (intraarticular)
• pathophys: impaired platelet production and destruction (T cell, B cell, spleen)
• Tx: steroids, IVIG, platelets (only when sick, will be destroyed anyway), splenectomy
• RhoGAM: induces mild hemolysis in Rh+ patients, spares igG coated platelets from splenic destruction
• New drugs: thrombopoietin receptor agonists, stimulates platelet production

TTP

• FATRN: Fever, MAHA, Thrombocytopenia, renal, neuro
• anemia, thrombocytopenia +/- neuro
• think TTP if anemia, thrombocytopenia, hematuria (intravascular hemolysis)
• uremia is rare
• wax and wane: platelet clot is unstable (becomes stable only when with fibrin)
• common: obese, black, female, HIV, drugs (quinine, plavix, ticlopidine)
• untreated: >90% mortality; treated: 10-20% mortality
• platelet worsens
• Pathophys: ADAMTS-13 (protease) is lacking which supposed to cleave vWF
• ULvWF, released from endothelium when stressed (trauma/infection), attaches to platelets = vWF monomers
• in TTP, platelet microthrombi (with no fibrin) = microangiopathic hemolytic anemia (increased uncon bilirubin, increased LDH, normal fibrin/fibrinogen)
• New tests: ADAMTS-13 level, activity, inhibitor, vWF gel electrophoresis, DNA analysis
• Huge spleen
• Tx:
• FFP: provides the protease but does not eliminate the inhibitor; if not improving, can double the dose
• PET: plasma exchange therapy -- definitive; eliminates the inhibitor
• Steroids, immunosuppressants
• IVIG, antiplatelets = no evidence and antiplatelet increases risk for bleeding
• NO PLATELETS! unless patient is dying from ICH

HUS

• usually kids: 6 mod - 4 years
• Triad: Thrombocytopenia + MAHA + ARF (vs TTP)
• 90% shiga-like toxin E coli 0157:H7
• STEC: endoth damage, thrombin generated, fibrin deposit, platelet-fibrin thrombin
• worsens, do not wax and wane due to fibrin
• high risk Hx: rare hamburger, petting zoo, unpasteurized fruits/juice, unchlorinated water, daycare, long-term care facility
• classic presentation: bacteria ingested (3 days) -> non bloody diarrhea (2 days) -> painful blood diarrhea -> platelet-fibrin clots -> thrombocytopenia, MAHA, ARF
• painful blood diarrhea = usually after FIVE days from ingestion of bacteria
• Dx: Presumptive; Stool for shiga toxin, urine for shiga toxin
• Lab: Thrombocytopenia, Hemolysis (schistocytes, UC bili, LDH, normal fibrin/fibrinogen, negative direct coombs), "negative" blood cultures for E. coli
• Tx: supportive, admission for IVFs, pRBC for Hb <6 or unstable VS, dialysis for anuria, resist urge for platelets (more platelet clots), antibiotics can increase toxin release

HIT: Heparin-induced Thrombocytopenia = BIG CLOTS

• 1-3% of heparin use, can occur with LMWH <1%
• Definition: Platelet <150K; >50% drop from baseline
• Type 1: hours-days
• Type 2: 4-14 days (mean day 9): most common
• Delayed onset: 9-40 days after heparin
• Antibody mediated; Heparin attaches to PF4/platelet factor 4 which initiates immune response
• S/S: Venous thrombosis (more common), Arterial thrombosis (less common), skin lesions, acute reactions, DIC
• Venous: presenting as DVT/PE (heparin underdose or HIT), adrenal thrombosis, cerebral venous/sinus thrombosis, venous limb gangrene
• Arterial thrombosis: limb artery, stroke, MI
• local skin lesions (common in clean): skin necrosis, erythematous plaques
• Diagnosis: 4Ts: Thrombocytopenia, Timing (5-14 days), Thrombosis, no oTher cause = complicated
• Tests: not done in ED, serotonin release assay, HI platelet aggregation assay, etc
• Tx: stop heparin, no platelets, no coumadin until platelet count is normal
• Change to direct thrombin inhibitor: lepirudin, argatroban, bivalirudin
• previous HIT, giving heparin is not c/i (anecdotally no recurrence)

DIC

• sepsis, malignancy, etc
• endothelial damage, systemic release
• Scoring system:
• Tx: cause, suportive

ALGORITHM for low platelet

• isolated low platelet: ITP (self-limiting in kids, in adults = insidious)
• heparin use + big clots: HIT (4Ts): no Heparin, no platelet, DTI
• high PT/INR, microvascular thrombosis, high fibrin/fibrinogen, sick: DIC: give plt
• + MAHA +/- CNS = TTP (waxing and wane, big spleen, plavix)
• + MAHA +/- ARF = HUS (pediatric, does not wax and wane)