UAMS Hematology Lab Exam 3

Normal range for PT

12.6-14.6 seconds (INR of 1)

Normal range for PTT

25-35 seconds

Normal range for Fibrinogen

220-498 mg/dL

Normal range for Thrombin Time

<21 seconds

Normal range for Bleeding Time

2-9 minutes

Normal range for Platelet Count

150,000-450,000 /uL

What factors are a part of the intrinsic system?

XII, XI, IX, VIII

What factors are a part of the extrinsic system?

III (tissue factor) and VII

What factors are a part of the common pathway?

X, V, II, I (and XIII?)

What tests test the common pathway?

PT, PTT, TT, and Fibrinogen

What are the vitamin K factors?

II, VII, IX, X

What are the consumable factors?

I, V, VIII, XIII

What factors are present in aged serum?

VII, IX, XI, XII

What factors are present in absorbed plasma?

I, V, VIII, XI, and XII

Factor I

fibrinogen

Factor II

Prothrombin

Factor III

tissue factor/thromboplastin

Factor IV

Calcium

Factor V

ProAcclerin/Labile Factor

Factor VII

Proconvertin, Stable Factor

Factor VIII

Antihemophilic factor (AHF)

What is VIII:C?

It is a smaller portion of the factor VIII molecule. It is also the coagulant portion of the molecule. A deficiency of this is termed Hemophilia A.

What is VIII:vWF?

It is a larger portion of the factor VIII molecule that serves as a carrier protein for VIII:C. This piece is necessary for platelet adhesion to collage.

- attaches collagen to glycoprotein IB on platelet surface.

What does the bleeding time, ristocetin aggregation, vWFR:Co, and vWF:Ag tests look like for Hemophilia A?

all normal

What does the bleeding time, ristocetin aggregation, vWFR:Co, and vWF:Ag tests look like for vWF disease?

all abnormal

What inheritance is Hemophilia A?

recessive, X-linked

What is the inheritance of vWF disease?

dominant, autosomal

What do platelet aggregation studies measure?

Measures primary aggregation and secondary aggregation when combined with various agonists such as ADP.

What does ADP do?

Encourages primary platelet aggregation, followed by a lag phase in which the platelets are undergoing shape change and secretion, followed by secondary aggregation. Abnormal ADP graph could indicate: Platelet membrane defect, aspirin use, or storage pool defect.

What does a normal platelet aggregation graph look like?

What does collagen do during platelet aggregation?

binds GPIa/IIa and GPVI but induces no primary aggregation.

What does an abnormal collagen graph indicate?

Aspirin use, storage pool defect, or release defect

What does epinephrine do during platelet aggregation?

binds to platelet receptors to activate platelets through the same pathway as ADP

What does an abnormal epinephrine graph indicate?

storage pool defect or membrane defect

What is ristocetin?

an antibiotic that encourages platelet aggregation in the presence of vWF. No aggregation will occur with ristocetin in vWF disease.

What happens when vWF and ristocetin are both present in vWF disease?

primary and secondary aggregation occur as normal

What does the platelet aggregation graph look like in vWF disease?

Notice there is no aggregation with ristocetin. Remember, ristocetin only allows for aggregation in the presence of vWF.

What does the platelet aggregation graph look like in Bernard Soulier Disease?

Bernard Soulier occurs when the GPIb complex is missing from the platelet surface.

- causes platelets to lack the ability to bind to vWF

- abnormal aggregation graph with ristocetin and ristocetin plus vWF

What does the platelet aggregation graph look like in Glanzmann's Thrombasthenia?

Defective platelet membrane GP IIb/IIIa.

- unable to bind to fibrinogen

- ristocetin has the ability to induce binding of vWF

What does the platelet aggregation graph look like in Aspirin Ingestion/Storage Pool (alpha or dense granule) defect?

ADP and Epinephrine will initiate a primary aggregation, but secondary aggregation does not occur. Low dose of collagen is unable to induce aggregation.

What does aspirin do to platelet aggregation?

aspirin inhibits cyclooxyrgenase, which converts arachidonic acid into Thromboxane A2, which is needed for storage granule secretion to enable secondary platelet aggregation

Factor IX

Christmas factor

Factor X

Stuart-Prower factor

Factor XI

Plasma Antecedent

Factor XII

Hageman factor

What is factor XII deficiency associated with?

CLOTTING!

Factor XIII

Fibrin-stabilizing factor (FSF)

What test is used to detect Factor XIII deficiency?

urea solubility test

- clots from normal patients are stable for 24 hours in solution

- Factor XIII deficient clots will dissolve rapidly

What will the lab results look like in DIC?

- decreased platelets

- Schistocytes on PB smear

- prolonged PT and PTT

- prolonged bleeding time

- decreased fibrinogen

- increased FSP and D-dimer

What is Thrombotic Thrombocytopenic Purpura (TTP)?

hyaline thrombi, composed of platelets and vWF, occurring in arterioles and capillaries

What is TTP caused by?

due to lack of ADAMTS-13 molecule that cleaves large vWF molecules.

What will lab results look like for TTP?

- decreased hemoglobin

- decreased platelets

- signs of hemolysis

- schistocytes on PB smear

- normal PT and pTT

- normal fibrinogen

- normal FSP and D-dimer

- associated with neurological manifestations

What is Immune Thrombocytopenic Purpura (ITP)?

an autoimmune disorder, results in platelet antibody formation and excess destruction of platelets

What do lab results look like for ITP?

- normal RBC morphology

- normal PT, PTT and Fibrinogen

- decreased platelet count

- prolonged bleeding time

- positive Platelet IgG Antibody Screen

What factors do protein C and S inhibit?

V and VIII

How is the protein C pathway activated?

by thrombin binding to thrombomodulin

What is anti-thrombin III?

serine protease inhibitor

What must heparin bind to in order to exert its anticoagulant effect?

anti-thrombin III

What is Factor V Leiden?

Mutated form of factor V that lacks cleavage site for deactivation by proteins C and S. Patient will be unable to stop the clotting process.

What are non-specific anticoagulant or antibody?

antibodies that are found in patients with auto inflammatory conditions (I.e. systemic lupus erythrematosus). Sometimes thought to be an antibody formed to receptors on the platelet membrane.

If patient plasma is mixed with normal plasma, and the PTT corrects, what is suspected?

Factor deficiency

If patient plasma is mixed with normal plasma, and the PTT does NOT correct, what is suspected?

Lupus anticoagulant or factor inhibitor

Hemophilia A

Factor VIII deficiency

Hemophilia B

Factor IX deficiency