VTE Prophylaxis - Prevention is best. At least one-third of hospitalized patients are at high VTE risk, they will require prophylactic

anticoagulation therapy. Pulmonary Embolism (PE)

- PE s/sx: Not too direct, but primary sx include chest pain, dyspnea, tachycardia, pass-out from hypoxemia, syncope

- PE Dx o Step 1: CT Pulmonary Angiogram – has high sensitivity and

specificity, it is the gold standard o Transthoracic Echocardiography (TTE): Noninvasive, TTE offers a

nice visualization of the heart to assess the RV and LV size, systolic function, and check for valvular abnormalities.

o Ventilation-Perfusion Scintigraphy (V/Q Scan): An older tool that gives 3 potential results, none of which are conclusive which is why it is no longer favored. It can rule out PE with a 0.9% failure rate.

- PE can be classified temporally into Acute, Subacute, and Chronic categories - PESI Scores

o Once dx with PE, a 30-day mortality risk can be calculated using the PESI scores

o £ 65: Low risk – consider outpatient therapy if clinically appropriate o > 65: High risk – patient will require close monitoring and potentially admittance into the ICU

(3/12) Kim Lecture: Heparin-Induced Thrombocytopenia Heparin-Induced Thrombocytopenia (HIT)

- Get injected with Heparin, there’s a few things that can happen - No Ab: Most patients receiving heparin will not form the antibody - Subclinical: A subset will form Ab, but not show symptoms - Thrombocytopenia: The next subset will have a significant depletion

of platelet, which is the first major concern and a thrombotic complication. Bleeding Risk

- Thrombotic Complication: Risk still elevated 4 weeks post-d/c o If untreated, the risk increases 50-89% o Mortality: 17-30% associated with severely low platelet

- Pathophysiology o Once exposed to heparin, circulating platelet factor IV (PF4) adheres to the heparin product o Complex formation stimulates production of IgG and other Ig against

Heparin-PF4 o IgG binding to Heparin-PF4 produces a substrate, IgG-Heparin-PF4, which

can activate platelets at the Fc receptor. Binding to the Fc receptor will cause the release of micro particles and pro-coagulants

o The micro particles can activate other platelets, leading to further PF4 release o Overall, this activity involves the burst generation of thrombin and may

damage the blood vessel - Clinical Presentation of HIT

o Venous: DVT, PE, Cerebral venous thrombosis, venous limb gangrene o Arterial: Limb artery thrombosis + amputation, thrombotic stroke, MI

- Risk Factors for Immune-mediated mechanism o Duration of heparin exposure (> 4 days), o Heparin type ~ Bovine > porcine, IV > SubQ, UFH > LMWH o Patient Population: Cardiac surgery, purpose for hospitalization (orthopedic > medical) o Gender: F > M

Isolated HIT HIT ± Thrombotic Syndrome Reversible – Not-immune mediated Fast onset, 1-2 days Transient reduction in platelet during Heparin therapy, occurring 10-20%

More serious, Immune-mediated Delayed onset, 5-10 days Characterized by ³ 50% drop in platelet count, which will recover upon d/c

Diagnosing HIT - Step 1: Clinical Sx: First Symptom = Thrombocytopenia - Step 2: 4T Scoring System: A non-invasive approach involving 4 categories, ranging 0 – 2 points

o (1) Thrombocytopenia: To what extent is the patient low? § Plateletß > 50% receives 2 points,

o (2) Timing of platelet count fall: Used to determine if the process is immune-mediated § ß on Days 5-14 days à 2 points, more likely immune mediated § ß in under 4 days without recent heparin exposure à 0 points, likely not immune-mediated

o (3) Thrombosis or other sequelae § New confirmed thrombosis, skin necrosis, or anaphylactic rxn à 2 points § No sequelae à 0 points

o (4) Other causes of thrombocytopenia: Definite other causes of [plateletß] is not a sign of HIT o TOTAL: 6-8 points = High probability, 4-5 intermediate, 0-3 low

- Step 3: Confirm with Lab Tests: Check out the antibodies using immune- or functional assays o Immune: Detects Ab against PF4/Heparin using ELISA. 95% sensitive, 50-89% specific o Functional: Detects Ab that induce Heparin-dependent platelet activation. Unfortunately, while these

tests boast up to 98% sensitivity and 95% specificity, it takes 5-7 days to develop. Serotonin is released when platelets activate, so functional serotonin assays (SRA) are ideal, but takes a while

§ à Serotonin release assays (SRA) are the gold standard lab test to confirm HIT dx Differential diagnosis for thrombocytopenia: Many conditions, events, and medications can cause thrombocytopenia, it is important for us to be aware of them as it constitutes part 4 of the 4T scoring system

- Conditions: Sepsis, bone marrow disorder, intravascular device~balloon pump - Events: Active bleeding, massive venous thromboembolism, pseudo-thrombocytopenia (lab fail) - Medication-Induced: Can be immune-mediated or not

o Immune-Mediated § Immune-Complex: Heparin § Hapten-dependent: Penicillin, Cephalosporin § Drug-dependent antibody: Quinine, NSAID, Sulfonamide § Platelet-specific autoantibody: Abciximab

o Non-immune-mediated § Bone marrow suppression (thrombopoiesis, megakaryocytes) ~antineoplastics § Dose-dependent, Delayed onset~weeks:

HIT Management - After confirming diagnosis, Document the Heparin Allergy in the EHR/EMR, alert the patient and family - Avoid Heparin x3months– this includes Heparin flush, heparin-coated catheters, and LMWH

o Even after d/c, the risk of HIT can last up to 4 weeks. The antibody lasts 50-85 days. o Therefore, re-exposure requires careful evaluation. It is advised to use an alternative anticoagulant o Heparin for a surgery doe? Delay surgery, confirm Ab are gone using ELISA

- Platelet Transfusion?: routine use is not recommended, it is reserved for severe thrombocytopenia with active bleeding or undergoing invasive procedures. Since this is a thrombotic reaction, you cannot give more platelet to increase your platelet count. It will lead to further thrombin formation and increase the patient’s risk

- Non-Heparin Anticoagulation Therapy [only argatroban and bivalirudin are FDA approved] o Direct thrombin inhibitors (DTI): Argatroban, Bivalirudin, Desirudin

§ Argatroban IV infusion: Short half-life, it requires more frequent aPTT monitoring (q2º) • Caution: Argatroban falsely elevates INR, a reading of 4 really means about 2

§ Bivalirudin IV infusion: Only for pt with Hx of HIT about to undergo PCI o Indirect Factor Xa Inhibitor: Fondaparinux ~ patient specific, some reports of HIT-like TS

- Vitamin K Antagonist (VKA): Warfarin ~ used for long-term anticoagulation o VKA initiation should be delayed until platelet > 150k o Patients with HIT-TS à 3 months of warfarin therapy o Patients with isolated HIT à 4 weeks of warfarin therapy

- Patient Education: Healthcare providers need to be made aware of the heparin allergy o Medical bracelet, wallet care – is useful and can prevent life-threatening rxns