Heparin Induced Thrombocytopenia (HITS)

Question 1

HITS Types

Answer 1

*HIT type I, a benign non-immune condition
*HIT type II, an immune-mediated syndrome caused by an antibody to the PF4/heparin complex

Incidence of HIT type II

1-5% with UFH
< 1% with LMWH
Heparin Induced Thrombocytopaenia Syndrome (HITS)
Heparin Induced Thrombosis with Thrombocytopaenia Syndrome (HITTS)

Question 2

Pathophysiology

Answer 2

Platelet Factor 4:
*PF4 is released on platelet activation -> binds anionic glycosaminoglycans on cell surfaces -> inhibit the formation of megakaryocytes and angiogenesis + modulate immune response.
PF4 is released after trauma, inflammation, surgical trauma, and in cancer

HIT Type I

*10-30% of patients within 4 days after exposure to heparin
*Heparin binds to PF4 -> decreases cAMP -> mild platelet aggregation and thrombocytopenia
*platelet counts rarely decrease below 100,000/μl
*mild and self-limiting

HIT Type II

1.*formation of a PF4/heparin complex -> triggers an immune response ->
*IgG binds PF4/heparin complexes -> *platelet activation ->
arterial and venous thrombosis
2HIT antibodies may bind to Fc receptors on monocytes -> tissue factor -> thrombosis
3.also endothelial damage -> increased von Willebrand factor and soluble thrombomodulin -> thrombosis

Not all patients who have heparin antibodies develop platelet activation and clinically relevant HIT

Question 3

clinical Features

Answer 3

Onset
*typically 5-10 days post heparin
-consider other causes if later than 10 days (especially sepsis, also drugs + others)
-rapid onset can occur if prior exposure to heparin (can mimic PE)
-delayed onset can occur after heparin stopped

Thrombocytopaenia
*usually falls to values between 40,000 to 80,000/μl
-<10% fall to <20,000
-Complications can occur before, or without, thrombocytopaenia

Question 4

Risk Factors and scoring system

Answer 4

*Risk factors
-amount of heparin exposure -
(therapeutic > prophylactic; UFH > LMWH)
-amount of PF4 release:
surgical and trauma patients > medical

*Scoring system for likelihood pretest probability – 4Ts

Thrombocytopaenia severity
Timing of onset of platelet decrease (recent exposure increases risk)
Thrombosis (recent proven increases risk)
Thrombocytopaenia due to other reasons likely?

Question 5

Investigations

Answer 5

Antigen assays – e.g. ELISA
-PF4/polyanion EIA–>
detects antibodies reactive against the PF4/Heparin complex (IgM, IgG and IgA)
IgG is the most sensitive for disease
high sensitivity (90-98%) and low specificity (65%) with positive result = 0.4 optical density untis
> 1.0 optical density units = more likely to be HIT (higher specificity ~83%)
increase in clinical condition thus delay until danaparoid or lepirudin is therapeutic and platelet count has recovered

*Functional assays
-Heparin-induced platelet activation (HIPA) and serotonin release assays
-very high specificity
-technically demanding (selected platelet donors, washed platelets, internal controls, radioactivity), high turn-around time, poor availability

Question 6

Complications

Answer 6

COMPLICATIONS
-venous thrombosis — DVT 50%, PE 25%, venous sinus thrombosis
-arterial thrombosis — arterial, mesenteric, stroke, MI, acute leg ischemia, etc
-skin necrosis at sites heparin is injected (usually ~8 days post-heparin starting)
-acute systemic reactions after IV bolus (may look like anaphylaxis or PE)
-decompensated DIC
-death (10-30%)

Question 7

Approach

Answer 7

APPROACH

1) stop heparin, including ‘heparin locks’ and coated catheters
2) avoid platelet transfusion
3) do not wait for laboratory confirmation if high degree of suspicion
-if uncomplicated and low degree of suspicion await laboratory confirmation

alternatives to heparin:
- direct thrombin inhibitors (e.g. lepirudin, bivalirudin) and factor Xa inhibitors (e.g. danaparoid, fondaparinux)
a positive ELISA alone does not mean the patient has HIT
- avoid warfarin in HIT until the platelet count has recovered (risk of thrombosis due to Protein C and S deficiency; risk of skin necrosis)