Hematology Ch. 15

hemostasis and platelet physiology

What is hemostasis?

the process by which the body spontaneously stops bleeding and maintains blood in a fluid form

involves blood vessels, platelets, and coagulation factors

What are the two systems of hemostasis (systems that contain blood and maintain fluidity)?

• primary hemostasis

  • involves the vascular system and platelets

  • activated by small vessel damage

• secondary hemostasis

  • involves clotting factors

  • activated by major trauma, surgery, or hemorrhage

What is vasoconstriction?

• the body’s immediate response to blood vessel injury

• helps minimize blood loss at the site of injury

Describe platelets. What is their size? What do they contain? Where do they come from? What happens when they are activated?

• size

  • 2-3 micrometers

• contains:

  • dense granules and alpha granules (instead of a nucleus)

• derived from:

  • megakaryocytes

• when activated:

  • platelets change shape and become small spheres

Where in the body can you find 1/3 of all platelets? What is the normal platelet count?

• 1/3 of all platelets are found in the spleen

• normal platelet count: 150,000-450,000 / uL

What are the 5 steps of platelet function in primary hemostasis?

1. adhesion

   1. platelets stick to endothelial cells (cells within blood vessels) that contain collagen

2. shape change

   1. platelets change shape when attached to collagen

3. secretion

   1. platelets release granules that promote aggregation

4. amplification

   1. secreted substances recruit more platelets

5. aggregation

   1. platelets stick together and form a plug

If primary hemostasis is abnormal, bleeding may occur when the platelet count is:

less than or equal to 40,000 / uL

How do Platelet Function Analyzers (PFAs) evaluate platelet function?

• by measuring closure time

  • the time it takes for blood to stop flowing because of the formation of a platelet plug in the body

• uses citrated whole blood

• epinephrine and ADP are used to induce platelet adhesion, activation, and aggregation

What happens in secondary hemostasis?

• hemostasis is maintained via coagulation factors

• inactive coagulation factors in the blood are converted to active enzymes that participate in the coagulation

Factor I is also known as ____ and Factor II is also known as ____

fibrinogen, prothrombin

Which factor stabilizes the fibrin clot at the end of the coagulation cascade?

Factor XIII (fibrin stabilizing factor)

What are the 4 big steps of the common pathway of the coagulation cascade?

1. injury

2. vasoconstriction

3. platelet plug (primary hemostasis)

4. coagulation cascade (secondary hemostasis)

What is the difference between the intrinsic pathway and the extrinsic pathway of the coag cascade?

• intrinsic pathway

  • intrinsic to the blood

    • something within the blood triggers the cascade

  • more steps, longer cascade (but more efficient)

• extrinsic pathway

  • triggered from outside the blood

  • depends on the factors from outside the blood

  • less steps, shorter cascade (less efficient though)

What 4 substances make up the prothrombinase complex, a complex that stimulates prothrombin to convert into thrombin?

• calcium

• membrane phospholipids

• Factor Va

• Factor Xa

What factors are found in the extrinsic pathway of coagulation?

VII, III (tissue factor), and IV (calcium)

What factors are found in the intrinsic pathway of coagulation?

XI, XII, IX, and VIII

What are the 9 steps of the extrinsic pathway of coagulation? (diagram in notes)

• tissue trauma/injury occurs

• tissue factor (aka tissue thromboplastin), released by tissues, enters the bloodstream

• tissue factor binds to Factor VII

  • which is free-floating in the blood

• Factor VII activates and turns into Factor VIIa

• Factor VIIa activates Factor X, Factor X turns into Factor Xa

• Factor Xa, along with activated Factor Va, calcium, and membrane phospholipids, form the prothrombinase complex (PTC)

• PTC causes prothrombin to convert into thrombin

• thrombin causes fibrinogen to convert into fibrin

• fibrin is stabilized by Factor XIIIa

What are the 5 steps of the intrinsic pathway of coagulation? (diagram in notes)

• internal trauma occurs, causing collagen in vessel walls to become exposed

• exposed collagen activates Factor XII, which turns into XIIa

• Factor XIIa triggers Factor XI to become Factor XIa

• Factor XIa triggers Factor IX to become Factor IXa

• Factor VIIIa triggers Factor X to become Factor Xa

• Xa and the rest of the PTC go through the common pathway, eventually forming a stable clot

Factor III is also known as ____ and Factor IV is also known as ____

tissue factor, calcium

What is the responsibility of anticoagulants in the coag cascade, and what are 3 common types?

• naturally limits coagulation

• deficiencies cause thrombosis

• types:

  • Protein C

    • natural thrombosis inhibitor

  • Protein S

    • thrombosis inhibitor

  • Activated protein C

    • inactivates factor Va and VIII to stop clotting

What is the purpose of fibrinolytic and antifibrinolytic factors?

• to lyse clots after they have been formed and bleeding has ceased

Prothrombin Time (PT) lab test

• measures extrinsic and common pathways of coagulation

• performed with reagents containing tissue factor, platelet phospholipid, and calcium

• used to determine Factor VII deficiency

• used for monitoring oral anticoagulant therapy or for the evaluation of acutely bleeding patients

What is the purpose of the international normalized ratio (INR) in monitoring anticoagulant therapy?

• INR is used to standardize PT results for monitoring anticoag therapy

• reduces variability between labs

  • uses a mathematical correction of PT values

  • INR = (patient PT/normal PT) ^ ISI

    • ISI is international sensitivity index

Activated partial thromboplastin time (APTT) lab test

• screens the intrinsic and common pathways of coagulation

• used to monitor therapy with unfractionated heparin

  • also screens for thrombotic disorders, evaluates liver disease, and ID coag abnormalities

• reagent contains phospholipid and an activator to initiate the intrinsic pathway

  • does NOT contain tissue factor, this is why it’s called partial

What are mixing studies?

• additional tests performed to evaluate abnormal PT or APTT results

• also used to identify a factor deficiency

• patient plasma is mixed 1:1 with normal plasma and the test (PT, APTT, or both) is repeated

How are mixing study results interpreted?

• if the PT is corrected

  • results fall into the normal reference range

  • patient has a factor deficiency, liver disease, vitamin K deficiency, or is undergoing anticoagulant therapy

• if the PT is NOT corrected

  • patient has a Factor V inhibitor

• if the APTT is corrected

  • patient has DIC, factor deficiency in the intrinsic system, vWD, vitamin K deficiency, or liver disease

• if the APTT is NOT corrected

  • patient has lupus anticoagulants or a factor VIII inhibitor

If a patient has a prolonged PT, the patient most likely has a deficiency in factor:

• VII

  • PT is used to identify factor VII deficiency

What 2 molecules cause vasoconstriction?

thromboxane A₂ and serotonin

Which coagulation factors are vitamin K-dependent?

II, VII, IX, and X

If a patient has a prolonged APTT only, the patient may be deficient in the factors:

VIII, IX, XI, and XII

• these are the factors found in the intrinsic pathway of coagulation

Protein C and its cofactor protein S inactivate factors:

Va and VIIIa