Coagulation Cascade

A prolonged Prothrombin time (PT) and prolonged activated partial prothrombin time (aPTT) is indicative of what?

1. Anticoagulants 2. Liver Disease 3. Factor X 4. Vitamin K Deficiency

What are coumadins?

1. Vitamin K antagonists

What are the symptoms of hemophilia?

Excessive bleeding 50% severe bleeds with dental surgery

A normal Prothrombin time (PT) and normal activated partial prothrombin time (aPTT) is indicative of what?

Normal vWD

The extrinsic pathway of blood clotting occurs when there is damage to _______.

The extrinsic pathway of blood clotting occurs when there is damage to TISSUE.

What is Vitamin K and how is it involved in blood coagulation?

Vitamin K is a cofactor in carboxylation of glutamate residues to form Factors II, VII, IX & X and anti-coagulant proteins C, S & Z.

What are the characteristics of vWf?

1. Constitutively secreted by endothelial cells 2. Secreted by activated platelets 3. Essential for platelet-collagen bond 4. Involved in platelet-platelet bond 5. Only in the 'soft clot' stage

Prophylaxis of Factor VII deficiency occurs when what drug is administered?

1. DDAVP (Desmopressin) 2. DDAVP releases all available Factor VII in the body

Describe the activation of the intrinsic coagulation pathway.

1. Damage exposes basement membrane collagen 2. Exposed collagen causes activation of Factor XII a.) Factor XIIa initiates the intrinsic coagulation pathway 3. Exposed collagen binds von Willebrand factor (vWf)

Describe the extrinsic pathway coagulation sequence.

1. Damaged tissue cells secrete Tumor Necrosis Factor (TNF) 2. TNF causes endothelial cells, vascular smooth muscle cells, and fibroblasts to externalize adhesion receptors 3. TF converts Factor VII to Factor VIIa 4. Factor VIIa converts Factor X to Factor Xa, activating the common pathway

What are some characteristics of Vitamin K?

1. Enteric bacteria make enough vitamin K (except in neonates). 2. Vitamin K is fat soluble, so deficiency is seen in fat mal-absorption (steatorrhea).

What are some common pathway factor deficiencies?

1. Factor V deficiency: rare, treat with Fresh Frozen Plasma* (FFP) 2. Factor X deficiency: rare, treat with Prothrombin Complex Concentrates (PCC) or FFP 3. Factor XIII deficiency: rare, treat with Factor XIII (Corifact) 4. Fibrinogen deficiency: treat with cryoprecipitate or FFP.

Describe the intrinsic pathway coagulation sequence.

1. Factor XIIa converts Factor XI to factor Xia 2. Factor XIa converts Factor IX to factor IXa 3. Factor IXa converts factor VIII to Factor VIIIa 4. Factor VIIIa activates the common pathway by converting Factor X to Factor Xa

Describe the common pathway coagulation sequence.

1. Factor Xa converts Prothrombin to thrombin 2. Thrombin converts Factor V to Factor Va, which assists in converting prothrombin to thrombin 3. Thrombin converts Fibrinogen to fibrin 4. Thrombin converts Factor XIII to Factor XIIIa

What are the characteristics of Type II vW disease?

1. Inherited and dominant 2. Less vWf and reduced ability for platelets to adhere to vWf 3. Mild-moderate treat with DDAVP, may need factor VIII concentrate

What are the characteristics of Type I vW disease?

1. Inherited and dominant 2. Usually includes Factor VIII deficiency 3. Treat with DDAVP (desmopressin) 4. Added Factor VIII helpful

What are the characteristics of Type III vW disease?

1. Inherited and recessive 2. Little to no vWf in the body 3. Treat with factor VIII concentrate

What is hemophilia?

1. Intrinsic pathway disorder 2. Hemophilia A (Factor VIII deficiency) 3. Hemophilia B (Factor IX deficiency) 4. A & B are X-linked, recessive

How do you treat a Factor VII deficiency?

1. Recombinant Factor VII (NovoSeven) "First line" 2. Prothrombin Complex Concentrate (PCC) "2nd line" 3. Fresh Frozen Plasma (FFP) - least effective & potential volume overload "2nd line"

How do you treat hemophilia?

1. Replacement factors 2. Vasopressin (Desmopressin/DDAVP) controls mild-to-moderate hemophilia A, but not B

How does liver disease effect blood clotting?

Both hypo- and hyper-coaguability can be present since the liver makes anti-coagulant factors AND pro-coagulant factors

Which clotting factor does the liver not make?

Factor VII

A prolonged Prothrombin time (PT) and normal activated partial prothrombin time (aPTT) is indicative of what?

Factor VII deficiency

Name one extrinsic pathway bleeding disorder.

Factor VII deficiency

A normal Prothrombin time (PT) and prolonged activated partial prothrombin time (aPTT) is indicative of what?

Factor VIII, IX, XI, XII deficiencies

What is the function of Factor XIIIa?

Factor XIIIa stabilizes cross links

What is the function of fibrin?

Fibrin cross links platelets

How are coagulation disorders assessed?

Prothrombin time (PT) and activated partial prothrombin time (aPTT or PTT) are used

What is the function of vWf?

Stabilizes platelet binding to collagen via a platelet membrane receptor

The intrinsic pathway of blood clotting occurs when there is damage to _______.

The intrinsic pathway of blood clotting occurs when there is damage to BLOOD VESSELS.

True or False. All types of von Willebrand disease cause bleeding.

True

True or False. Vitamin K and its analogues are also used to treat warfarin overdose.

True

True or False. vFw is involved in the the activation of the intrinsic pathway.

True

True or False. In the intrinsic blood clotting pathway, Factor XII is converted to Factor XIIa.

True. Factor XII (inactive) is converted to Factor XIIa (active).

What are the types of von Willebrand disease?

Type I (common) Type II (less common) Type III (rare)