Hospitalized patient with clot after week in hospital
Type:
HIT -1 (antibody present but not clinically significant)
HIT - 2 (true HIT)
Autoimmune HIT (Rare; usually after major surgery)

Sepsis (meningococcus, pneumococcus), metabolic stress, obstetrical complications, malignancies APML, burns

Occurs at any age; peaks in third decade
More common in females (60%)

Children, 2-6, associated with prior viral illness, spontaneous resolution, supportive mgmt
Adults, associated with SLE, HIV, thrombocytopenia <20k, mucosal bleeding

Activated Platelet (by surgery or infection) release PF4 from alpha-granule
PF4/Heparin polyanion complex is formed OR
PF4/ Bacteria polyanion complex is formed
This complex activates B cell and produce IgG against PF4
Ig G ab - PF4/Polyanion complex is formed
This complex binds platelets and activates more platelets - causes increased thrombosis
Monocytes also activates them - causes thrombosis
Platelet bound with Anti-PF4 ab are removed by splenic macrophages leading to thrombocytopenia
Hence, unlike all other cause of thrombocytopenia that causes bleeding, HIT paradoxically causes thrombosis.

Release of TF, endothelial damage, endotoxin, exposure of procoagulants from cancer cells. Production of thrombin and activation of fibrinolytic system. Clots using up coagulation factors.

Normally, endothelial cells produce ultra-large von Willebrand factor (vWF) multimers which is cleaved by ADAMTS13
With deficiency, large vWF multimers are in circulation, bind platelets and cause microthrombi in circulation
• Can be enhanced by other factors (drugs, hypertension, post-partum) that damage endothelial cells

Acquired autoimmune disorder, antibodies against platelet membrane glycoproteins from meds, viral infection, pregnancy, autoimmune disorders

4T scoring (0-2 point for each) NEJM 2015
Acute Thrombocytopenia (usually >20K)
10 % have decrease in platelet count of 30-50%
Timing of Onset (Day 5-10, <5 days, >10 days)
Only exception is if patient was on heparin in near past.
Rapid-onset HIT (within 30 min)
Delayed-onset HIT (unto 3 weeks after)
New Thrombosis
VTE occurs in 50% of confirmed HIT
Alternative cause of thrombocytopenia (DIC, Drugs etc)
Score:
6-8: High probability. Order further tests.
4-5: Intermediate score.
<3 : 5% probability.

Platelets Low
Fibrinogen Low
D-Dimer Increased
PT/PTT Increased
FVIII Decreased
MAHA Schistocytes

• Fever
• Microangiopathic hemolytic anemia
• Thrombocytopenia
• Renal abnormalities
• Neurological changes

Thrombocytopenia with normal marrow
Diangosis of exclusion, PT and PTT normal

Screen: ELISA ab.
If positive, reflexively, optical density test for quantification.
If that is positive, Serotonin Release Assay (SRA)
Gold standard for diagnosis.
Negative SRA does not exclude HIT

Treat underlying cause
• Supportive care (maintain BP, etc.)
• Replacement therapy for bleeding (FFP, cryoprecipitate and platelet transfusions)

• Schistocytes -Intravascular hemolysis – peripheral smear
• Platelets < 20K
• Increased reticulocyte count
• Increased indirect bilirubin
• Increased LDH
• Decreased haptoglobin
FIBRINOGEN AND D-DIMER NORMAL-HYALINE CLOT

Steroids –reduce the rate of platelet destruction
• Other immunosuppressive drugs (eg, rituximab)
• IVIG – Intravenous Immuno(gamma) globulin
• Rh Immune globulin (RhoGAM) – Spleen removes Ab coated RBCs from circulation rather than plt (in RH + people)
• Splenectomy
• Stop suspected medicine if possible
• Treat infection
• Thrombopoiesis-stimulating drugs offer a new treatment option
• Plt (if life threatening)

Direct Thrombin Inhibitor
Lepirudin (FDA approved)
Argatroban (FDA approved)
Off label use of Fondaparinaux as Fondaperinaux does not have moiety to cause antibody production, yet can activate anti-thrombin.
Use therapeutic dose anti-coagulation until platelet > 150K for 2 consecutive days.
Avoid the use of warfarin. Decrease APC, procoag.

DIC with fibrin strands in small BVs that slice up the RBCs
• Schistocytes also present in TTP and HUS; also present in artificial heart valves; also seen in APML (acute promyelocytic leukemia)

PLEX 1.5 volumes x 5 days (PLASMIC SCORE >=6)
FFP 2 units
Steroids (60mg pred, 125 sol)

Keep it chillllllllllll