Coagulation Lecture Notes

Flashcards for vocabulary review of coagulation lecture notes.

Coagulation

The process by which blood changes from a liquid to a gel, forming a clot.

Preoperative evaluation for bleeding risk

Includes history, physical examination, and appropriate lab testing to identify patients at risk for bleeding.

Primary Hemostasis

The first stage of hemostasis, involving platelet activation and adhesion to the injured vessel wall, forming a platelet plug.

Secondary Hemostasis

The second stage of hemostasis, involving the formation of a fibrin clot to reinforce the platelet plug.

Fibrinolysis

The process by which clots are broken down once tissue repair begins, maintaining blood fluidity during coagulation.

vWF (von Willebrand factor)

A protein that stabilizes the interaction between platelets and the subendothelial collagen layer of a damaged vessel.

TXA2 (Thromboxane A2)

A potent vasoconstrictor that promotes platelet aggregation.

ADP (Adenosine diphosphate)

A substance released from platelet granules that alters the membrane glycoprotein IIb/IIIa, facilitating fibrinogen binding to activated platelets.

Intrinsic coagulation pathway

A coagulation pathway occurring within the blood vessel, triggered by the interaction between subendothelial collagen and circulating factors (XII, high-molecular-weight kininogen, and prekallikrein).

Extrinsic coagulation pathway

A coagulation pathway beginning with the release of tissue thromboplastin (factor III) from the membranes of injured cells.

Tissue Plasminogen Activator (tPA)

An enzyme that converts plasminogen to plasmin, which degrades fibrin and fibrinogen into small fragments.

Prostacyclin (Prostaglandin I2)

A potent vasodilator that inhibits platelet activation and helps confine primary hemostasis to the injured area.

Antithrombin III

A coagulation inhibitor that complexes with and deactivates circulating coagulation factors (except factor VIIa).

Protein C

A coagulation inhibitor that inactivates factors Va and VIIIa.

Protein S

A coagulation inhibitor that augments the activity of protein C.

Tissue Factor Pathway Inhibitor

A coagulation inhibitor that antagonizes factor VIIa.

Thrombocytopenia

Defined as a platelet count of less than 150,000/mm3.

Minimal recommended platelet count before surgery

75,000/mm3

Normal bleeding time range

4 to 9 minutes

Aspirin's anticoagulant mechanism

Inhibits platelet cyclooxygenase, impeding production of TXA2 and inhibiting platelet aggregation.

Factor VIII

A large protein complex consisting of vWF (factor VIII:vWF) and factor VIII antigen.

Vitamin K's role in coagulation

Required for carboxylation of clotting factors (II, VII, IX, and X), allowing them to bind to phospholipid surfaces.

Heparin's anticoagulant mechanism

Accelerates the interaction between antithrombin III and the activated forms of factors II, X, XI, XII, and XIII.

PTT (Partial Thromboplastin Time)

Measures the clotting ability of all factors in the intrinsic and common pathways except factor XIII.

aPTT (Activated Partial Thromboplastin Time)

A modified PTT test with maximal activation of contact factors (XII and XI) for more consistent results; normal range is 25 to 35 seconds.

ACT (Activated Clotting Time)

A test where fresh whole blood is added to a test tube containing an activator, widely used to monitor heparin therapy in the operating room; normal range is 90 to 120 seconds.

PT (Prothrombin Time)

Measures the extrinsic and common pathways of coagulation.

INR (International Normalized Ratio)

A standardized measurement of prothrombin time, calculated as (PTpatient/PTnormal-ISI).

FFP (Fresh Frozen Plasma)

Should be considered when microvascular bleeding is noted and PT or PTT exceeds 1.5 the control value; also reverses the anticoagulant effects of warfarin.

Cryoprecipitate

The cold-insoluble white precipitate formed when FFP is thawed; contains factor VIII, vWF, fibrinogen, and factor XIII.

DIC (Disseminated Intravascular Coagulation)

A clinical complication in which clotting pathways are activated, leading to thrombin generation and fibrinolysis.

d-dimer

A neoantigen formed by the action of thrombin in converting fibrinogen to cross-linked fibrin.

Recombinant factor VIIa (NovoSeven)

Complexes with tissue factor to activate factors IX and X, used in hemophilia, liver transplantation, major trauma, and other bleeding conditions.

Thromboelastography (TEG)

Measures the viscoelastic properties of blood as it is induced to clot in a low shear environment, providing a measure of clot strength and stability.

TEG Parameter: R

Period of time from the initiation of the test to initial fibrin formation.

TEG Parameter: k

Time from the beginning of clot formation until the amplitude of TEG reaches 20 mm, representing the dynamics of clot formation.

TEG Parameter: Alpha angle

Angle between the line in the middle of the TEG tracing and the line tangential to the developing body of the tracing, representing the kinetics of fibrin cross-linking.

TEG Parameter: MA (maximum amplitude)

Reflects the strength of the clot, which depends on the number and function of platelets and their interaction with fibrin.

TEG Parameter: MA60

Measures the rate of amplitude reduction 60 minutes after MA, representing the stability of the clot.

Acceptable preoperative platelet count

150,000 to 440,000/mm3

Inherited Qualitative Platelet Disoders

von Willebrand disease

Acquired Qualitative Platelet Disorders

uremia, cirrhosis, medications (e.g., aspirin, NSAIDs])

Medications with Anticoagulant Potential

Nonsteroidal antiinflammatory drugs [NSAIDs], antiplatelet drugs, and anticoagulants

Drugs as a cause of Decreased Platelet Production

chemotherapy, cytotoxic drugs, ethanol, hydrochlorothiazide

Increased Peripheral Destruction of platelets is caused by:

hypersplenism, disseminated intravascular coagulation (DIC), extensive tissue and vascular damage after extensive burns, or immune mechanisms (e.g., idiopathic thrombocytopenic purpura, drugs such as heparin, autoimmune diseases)

Treatment for von Willebrand disease

Cryoprecipitate

Cryoprecipitate lacks:

Factor V (5), so treatment of DIC requires FFP.

DIC is NOT a disease entity, rather a clinical complication of other problems, such as:

Obstetric conditions (e.g., amniotic fluid embolism, placental abruption, retained fetus syndrome, eclampsia, saline-induced abortion), Septicemia and viremia (e.g., bacterial infections, cytomegalovirus, hepatitis, varicella, human immunodeficiency virus), Disseminated malignancy and leukemia, Transfusion reactions, crush injury, tissue necrosis, and burns, Liver disease (e.g., obstructive jaundice, acute hepatic failure)

DIC diagnostic tests

PT and PTT are elevated, and platelet count is reduced. Hypofibrinogenemia is common. In 85% to 100% of patients, FDPs are elevated. One measured form of FDP is the d-dimer.

Usual dose of FFP:

10 to 15 ml/kg

DIC treatment

treat the underlying disease process. Blood components are often depleted and require repletion based on tests of coagulation. Occasionally, if bleeding persists despite conventional treatment, antifibrinolytic therapy with ε-aminocaproic acid should be considered, but only if the intravascular coagulation process is under control and residual fibrinolysis continues.

Acceptable PTT

about 40 to 100 seconds; >120 seconds is abnormal.

Acceptable PT

10 to 12 seconds.

Primary treatment for DIC

to treat the underlying medical condition

Most common intraoperative bleeding diathesis

dilutional thrombocytopenia

Coagulation In-Vivo is initated by:

contact of factor VII with extravascular tissue.

Value of preoperative coagulation studies in asymptomatic patients

of little value

Thromboelastography (TEG) measures:

a dynamic test of clotting and can be as useful as all other clotting tests combined.

4 Clotting Factors synthesized by the Liver

II, VII, IX, and X

Platelet plug construction

ADP alters the membrane glycoprotein IIb/IIIa, facilitating the binding of fibrinogen to activated platelets.

INR therapeutic dosage range Standard/High:

Recommended therapeutic ranges for standard oral anticoagulant therapy and high-dose therapy, respectively, are INR values of 2 to 3 and 2.5 to 3.5.

Function of Fibrinolytic System

activated simultaneously with the coagulation cascade and functions to maintain the fluidity of blood during coagulation. It also serves in clot lysis once tissue repair begins.

Platelet count for severe intraoperative bleeding:

40,000 to 70,000/mm3

Platelet count for spontaneous bleeding:

counts <20,000/mm3

Normal aPTT:

25 to 35 seconds

When does the effect of Aspirin begin on Platelets inhibiting platelet aggregation?

within 2 hours of ingestion. Because platelets lack a cell nucleus and cannot produce protein, the effect lasts for the entire life of the platelet (7 to 10 days).

In von Willebrand disease, there is a decrease of both:

factor VIII antigen and factor VIII:vWF.

How does heparin affect platelet count?

Heparin may also affect platelet function and number through an immunologically mediated mechanism.