HEME: L10 Heparin-Induced Thrombocytopenia

Heparin-Induced Thrombocytopenia:

• … but serious adverse effects of heparin

• …-mediated (antibody) reaction

• Primarily a … (as opposed to bleeding) disorder

• .. types of HIT

  • Type … occurs up to ~5% of patients receiving … for > 4 days < 1% of patients receiving …

  • Mortality of type II HIT is ~…%

Rare, Immune, clotting, Two, II, UFH, LMWH, 20-30

Non-drug causes of thrombocytopenia:

• …/healthcare-associated infections

• … infections (e.g. HCV, HIV)

• …/some types of anemia

• Acute … deficiency

• Splenomegaly

• Excess … consumption

• Chronic … disease

• … (e.g. idiopathic thrombocytopenia purpura)

• Thrombotic thrombocytopenia purpura

• Hemolytic uremic syndrome

Sepsis, Viral, Leukemia, folate, alcohol, liver, Immune

Drug causes of thrombocytopenia (4 main ones):

Carbamazepine, Heparin, Rifampin, and Trimethoprim-Sulfamethoxazole

Type I HIT:

• Occurs in up to …% of patients receiving heparin

• Transitory (…), mild, and benign

• Due to … of platelets, which are still …

• Occurs within … days of heparin exposure

• Platelet count usually > … x 10⁹/L

• No heparin …

• No …

• Continue heparin

25, self-limiting, clumping, functional, 1-4, 100, antibodies, thrombosis

Type II HIT:

• Immune-mediated platelet … following heparin exposure

• Paradoxical … state

• Thrombotic complications occur in …% patients

• Can cause …-threatening or …-threatening thromboses

• More likely to cause … (e.g. DVT, PE) vs … (e.g. limb) thrombosis

• Occurs … days after heparin exposure

• Platelet count decreases by > …% (even if platelet count > 150 × 10⁹/L)

• Can occur abruptly in patients with recent (< … days) heparin exposure (especially < 30 days)

• Abruptly discontinue all heparin products and initiate … anticoagulant

activation, prothrombotic, life, limb, venous, arterial, 5-10, 50, 90, non-heparin

Risk factors of Type II HIT:

• Incidence with … is >10x than with …

• More common in … vs … surgery

• Women … risk than men

UFH, LMWH, major, minor, higher

HIT Pathophysiology:

• Development of heparin-dependent, platelet-activating … antibodies

• … (PF4) binds to heparin to form a complex → recognized as … → leads to development of anti-PF4-heparin antibodies

• Antibodies activate platelets and trigger a … state → excessive … generation

IgG, Platelet factor 4, foreign, prothrombotic, thrombin

HIT Presentation:

• Thrombocytopenia or acute drop in … count

• … venous or arterial thrombosis while on heparin

• Can also cause heparin-induced skin …, limb gangrene and acute … reactions (e.g., chills, dyspnea, respiratory or cardiac arrest)

• Bleeding is very …

platelet, New, lesions, systemic, infrequent

HIT Diagnosis:

• Based on ≥ …% drop in platelet count or thrombosis … days after starting heparin

• Normal platelet range … x 10⁹/L

• Typical nadir is … x 10⁹/L

  • Nadir could potentially be within the normal range

• Use 4T score for clinical …

  • Predictive value (positive or negative): probability that the disease is present/absent after obtaining a positive/negative test

50, 5-10, 150-400, 40-80, probability

4T Score:

• It is a validated clinical … tool

• 4T:

  • … of onset

  • … magnitude/degree

  • …

  • … causes of thrombocytopenia

prediction, Timing, Thrombocytopenia, Thrombosis, Other

How many points is considered high clinical probability of HIT based on the 4T score?

6-8

How many points is considered intermediate clinical probability of HIT based on the 4T score?

4-5

How many points is considered low clinical probability of HIT based on the 4T score?

0-3

The 4T score is better at ruling … HIT than ruling … HIT

out, in

Based on the 4T score, action is dependent on clinical scenario:

• Low probability → … required

• Intermediate probability → order … test ± … heparin and start non-heparin anticoagulant

• High probability → … heparin and start non-heparin anticoagulant ± order … test

no action, laboratory, discontinue, discontinue, laboratory

What is a first-line confirmatory laboratory test for HIT?

Latex immunoturbidimetric assay (LIA)

Goals of therapy for HIT:

• Prevent …

• Prevent … (e.g. loss of a limb)

• Prevent … (i.e. avoid heparin)

• … laboratory value (platelet count)

mortality, morbidity, recurrence, Normalize

Treatment for HIT:

• … heparin

• Therapeutic options:

  • …

  • … (off-label)

  • Others: …, … (off-label)

Discontinue, Argatroban, DOACs, danaparoid, fondaparinux

Argatraoban:

• … thrombin inhibitor

• Administered via …

• Target: …x baseline aPTT (also elevates INR)

• Duration:

  • Without thrombosis: …

  • With thrombosis: …

Direct, IV infusion, 1.5-2.5, 4 weeks, 3 months

Advantages of DOACs:

• Do not activate platelet … in presence of … antibodies

• … administration

• … onset

aggregation, anti-PF4-heparin, Oral, Rapid

What is the most commonly used DOAC for HIT?

Rivaroxaban

Type II HIT is a … to future UFH

contraindication