Thrombotic Disorders and Laboratory Assessment

Flashcards for reviewing vocabulary related to thrombotic disorders and their lab assessment.

Thrombosis

Inappropriate formation of a platelet or fibrin clot that obstructs a blood vessel.

Thrombosis Etiology

A multi-faceted disorder resulting from circulatory stasis or abnormalities that may affect primary hemostasis, secondary hemostasis, and fibrinolysis.

Deep Vein Thrombosis (DVT)

Most prevalent form of Venous Thromboembolism (VTE) caused by clots in the iliac, popliteal, and femoral veins of the calves and upper legs.

Thrombosis Symptoms

Localized pain, the sensation of heat, erythema (redness), and edema.

Emboli

Fragments of thrombi that may separate from the proximal end of a venous thrombus; may cause pulmonary emboli (PEs).

Unstable Atherosclerotic Plaque

Embedding of activated platelets, monocytes, and macrophages in the fatty plaque within the endothelial lining.

White Thrombi

Activated platelets which combine with von Willebrand factor to form arterial platelet plugs.

Thrombophilia (Hypercoagulability)

Predisposition to thrombosis secondary to a congenital or acquired condition.

Acquired Non-Disease Risk Factors (Thrombosis)

Age, Immobilization, Diet, Lipid Metabolism Imbalance, Oral Contraceptives.

Acquired Disease Risk Factors (Thrombosis)

Antiphospholipid Syndrome, Myeloproliferative Neoplasm, AML M3, Adenocarcinoma, PNH, Chronic Inflammation.

Congenital Risk Factors (Thrombosis)

mutation of specific amino acids which result in an abnormal protein function, affecting the control proteins in the coagulation cascade

Most common inherited thrombosis risk factor

FVL gene mutation

Important Notes in Testing Thrombophilia

Experts discourage thrombosis risk testing immediately after a thrombotic event because anticoagulant therapy and ongoing or recent thrombotic events interfere with the interpretation of AT, PC, PS, factor VIII, and LAC testing results.

Antiphospholipid Antibodies (APAs/APLAs)

Family of immunoglobulins that bind protein-phospholipid complexes; arise as immunoglobulin M (IgM) or IgG isotypes.

Lupus Anticoagulants (LACs)

Detected by clot-based profiles; an important first step in the LAC laboratory workup to establish the presence of an LAC.

Clinical Consequences of APLAs

Autoantibodies that arise in collagen vascular diseases; 50% of patients with SLE have autoimmune APLAs.

Antiphospholipid Syndrome (APS)

Transient ischemic attacks, Strokes, coronary and peripheral artery disease, Venous thromboembolism, Recurrent pregnancy complications, including spontaneous abortions

Guidelines for LA detection (2009 ISTH)

Characterized by prolong phospholipid-dependent clot formation using screening assay such as low phospholipid PTT or DRVVT

Anticardiolipin Antibody (ACA)

Antibodies directed at cardiolipin are mainly associated with infection, and patients with APS have 𝛽2-GPI bound to cardiolipin as the antigenic target

The ACL Test

Assay that is not affected by anticoagulant therapy, current thrombosis, or factor deficiencies.

Activated Protein C Resistance (APC)

A mutation in the factor V gene substitutes glutamine for arginine at position 506 of the factor V molecule (FV R506Q).

Prothrombin Assay G20210A

A guanine-to-adenine mutation at base 20210 of the 3’ untranslated region of the prothrombin (factor II) gene; increased risk of thrombosis is related to the elevated prothrombin activity.

Antithrombin (AT)

Serine protease inhibitor (SERPIN); neutralizes factors IIa (thrombin), IXa, Xa, XIa, and XIIa.

Dilute Russell Viper Venom Time (DRVVT)

Most sensitive/reliable detection method in LAC detection

Lipoprotein (a)

Marker used for Potential arterial thrombosis, may contribute to thrombosis by its antifibrinolytic property.

Homocysteine

Fasting homocysteinemia is an independent risk factor for arterial thrombosis.

Cardinal symptoms for DVT

Edema, Erythema, Pain, Sensation of heat

Pulmonary Embolism (PE)

Occurs when blood clot (thrombus) in the deep venous system of the lower extremities are lodged in an artery in the lung and blocks blood flow

Plasma D-Dimer

Chosen over imaging for low or intermediate DVT/PE pre-test probability scores, because of its robust sensitivity and negative predictive index

Disseminated Intravascular Coagulation (DIC)

Acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes

Acute DIC

Sudden exposure of blood to procoagulants generates intravascular coagulation

Chronic DIC

Liver coagulation factor production and bone marrow platelet production incompletely compensate for consumption

Malignancies Most Associated with DIC

Pancreatic, Prostatic, Ovarian, Lung Cancers, Multiple Myeloma

Heparin Induced Thrombocytopenia (HIT)

Heparin-PF4 complex is a hapten that triggers the immune production of IgG isotype antibodies.

HIT type I

Benign form of thrombocytopenia that develops 1 – 3 days

HIT type II

Thrombotic form that develops after 5 days

PTT, ACT, Ecarin Clotting Time, Plasma-Diluted Thrombin Time

Tests used to monitor the direct thrombin inhibitors for HITTS