Coagulation and Bleeding Disorders

Question 1

What are the 3 major components of the hemostatic system?

Answer 1

Vascular wall
Platelets
Coagulation Proteins

Question 2

What are the 3 phases of primary hemostasis?

Answer 2

Adhesion
Activation
Aggregation

Question 3

Adhesion

Answer 3

Adhesion of platelets to the damaged endothelial wall

Adhesion activates surface membrane receptors and adhesive proteins (vWF)

Question 4

von Willebrand Factor

Answer 4

Mediates the adherence of platelets to the subendothelial colalgen

Question 5

Activation

Answer 5

In order to effectively form a hemostatic plug, additional platelets are recruited to the local site
As platelets are activated by binding to vWF, there is release of second messenger molecules within the platelet

Question 6

What does platelet activation lead to?

Answer 6

Shape change of platelet from discoid to spheroid
Secretion of cytoplasmic ADP
Activation of the glycoprotein IIb/IIIa receptor
Contraction of the platelet mediated through actin fibers

Question 7

Activation

Answer 7

Platelets interact with other platelets
The release of cytoplasmic ADP causes the activation of adjacent platelets, and platelet-platelet binding through fibrinogen

Question 8

Secondary Hemostasis / Fibrin clot formation

Answer 8

Soluble coagulation proteins within the plasma are activated to generate thrombin in an amplification reaction
Thrombin converts fibrinogen to fibrin, which adds stability to the clot after fibrin monomers are cross-linked by Factor XII

Question 9

Intrinsic Pathway

Answer 9

Sequence of activation of Factor XII
XII –> XIIa (via kallikrein)
XI –> XIa (via XIIa)
IX –> IXa (via XIa)

Question 10

Extrinsic Pathway

Answer 10

Sequence of activation of Factor VII by TF:

VII –> VIIa (via TF)

Question 11

The Common Pathway

Answer 11

X –> Xa
Prothrombin –> Thrombin (via Xa)
Fibrinogen –> Fibrin (via thrombin)

Question 12

What proteins are responsible for regulating hemostasis?

Answer 12

Antithrombin
Protein C
Plasminogen

Question 13

How does Antithrombin regulate hemostasis

Answer 13

Inhibits the activity of thrombin and other serine proteases of the coagulation cascade, but forming an inactive enzyme-inhibitor complex

Question 14

What is the most well known Antithrombin and how does it work?

Answer 14

Antithrombin III
In the presence of heparin, it becomes activated so that it can form a complex with thrombin, thus destroying the ability of thrombin to participate in the coagulation cascade

Question 15

Protein C

Answer 15

Regulates major cofactors of the coagulation cascade (Va and VIIIa)
Activated Protein C (APC) plus Protein S (its cofactor) together inactivate factors Va and VIIIa

Question 16

Plasminogen

Answer 16

Gets activated by tissue plasminogen activator from the endothelium (tPA) into Plasmin
Plasmin trims fibrin, thus controlling the degree of secondary coagulation

Question 17

Prothrombin time (PT)

Answer 17

Time needed for plasma to form a clot in the presence of added tissue thromboplastin
Screens for the activity of proteins in the extrinsic pathway
Used to measure anticoagulation of pts using oral anticoagulants

Question 18

Partial Thromboplastin Time (PTT)

Answer 18

A measurement of the time needed for plasma to form a clot in the presence of added ground glass or kaolin (these activate Factor XII)
Screens for activity within the Intrinsic Pathwys

Question 19

Platelet count

Answer 19

A measurement of platelet number in anticoagulated blood

Normal: 150,000-400,000/uL

Question 20

Thrombocytopenia

Answer 20

Decrease in platelet number

Question 21

Thrombocytosis

Answer 21

Increase in platelet number

Question 22

Thrombocythemia

Answer 22

Increase in platelet number

Question 23

Mixing Studies

Answer 23

Measures platelet function
If pt has prolonged PT or PTT, you mix their blood with normal blood in a 1:1 ratio
If the problem is corrected - a deficiency exists
If the problem persists - there is an inhibitor present

Question 24

von Willebrand disease symptoms

Answer 24

Mucocutanous bleeding is the predominant clinical manigestation:
Nosebleeds
Ecchymosis (bruising)
Bleeding with trauma or surgery
Excessive menstrual flow

Question 25

von Willebrand Disease

Answer 25

Autosomal dominant abnormal vWF Most common inherited bleeding disorder Symptoms often improve after adolescence

Question 26

Type I vWF disase

Answer 26

Most common form | Decreased production in the amounts of vWF

Question 27

Type II wWF disease

Answer 27

Qualitatively abnormal vWF

Question 28

Type III vWF disease

Answer 28

Complete lack of vWF | This form is autosomal recessive

Question 29

What are the laboratory manifestations of vWF disease?

Answer 29

Prolonged PT | Prolonged PTT

Question 30

What are the therapeutic options for vWF disease?

Answer 30

Desmopressin Antifibrinolytic agents in mild cases Factor VII concentrates containing vWF and cryoprecipitate in severe cases

Question 31

What is the cause of Hemophilia A?

Answer 31

X-Linked Recessive Decreased Production of Factor VIII It's the most common cause for serious bleeding

Question 32

Clinical Manifestations of Hemophilia A?

Answer 32

``` Recurrent soft tissue bleeding Hemarthrosis Bleeding with trauma Intramuscular hematomas Intracranial hematomas Bleeding into other tissues ```

Question 33

Laboratory features of Hemophilia A

Answer 33

Normal PT Prolonged PTT Decreased Factor VIII

Question 34

Severe Hemophilia A

Answer 34

Factor VIII level of

Question 35

Moderate Hemophilia A

Answer 35

1-5% Factor VIII | Bleeding with minor trauma

Question 36

Mild Hemophilia A

Answer 36

>5% Factor VIII | Bleeding with major trauma

Question 37

How does Hemophilia B compare to A?

Answer 37

Clinical and lab presentation is similar to the deficiency of Factor VIII in Hemophilia A

Question 38

What causes Hemophilia B?

Answer 38

X-linked Recessive | Deficiency in Factor IX

Question 39

What three diseases cause Thrombocytopenia

Answer 39

ITP TTP DIC

Question 40

Bleeding due to Thrombocytopenia looks like what?

Answer 40

Petechial hemorrhages in the skin an mucous membrane

Question 41

Immune Thrombocytopenia Purpura

Answer 41

Immune-mediated destruction of platelets Platelets are coated with antibodies and sequestered in the spleen High mortality rate if left untreated

Question 42

Acute/Childhood Immune Thrombocytopenia Purpura (ITP)

Answer 42

``` Occurs in childhood Sudden onset Severe thrombocytopenia Often self-limited and resolves in 2-6 weeks Males and females are effected equally ```

Question 43

Chronic/Adult Immune Thrombocytopenia Purpura (ITP)

Answer 43

``` More typical in adults Gradual onset Moderate thrombocytopenia (much less than acute form) Doesn't resolve w/o treatment More common in females ```

Question 44

Clinical Features of ITP

Answer 44

Petechial hemorrhages Ecchymoses Bleeding with trauma or surgery

Question 45

Pathophysiology of ITP

Answer 45

Autoantibodies directed at the platelet membrane antigens GP Ib/IX and IIb/IIIa are common targets Increased IgG bound to the platelet surface promotes increased destruction by the reticuloendothelial system

Question 46

Thrombotic Thrombocytopenic Purpura cause

Answer 46

Intravascular platelet activation with formation of platelet-rich microthrombi throughout circulation Due to deficiency of ADAMTS 13 - which normally degrades very high molecular weight vWF

Question 47

Disseminate Intravascular Coagulation

Answer 47

Unregulated, widespread intravascular activation of the hemostatic system and systemic formation of thrombi and plasmin with simultaneous microthrombi formation and consumption of clotting factors

Question 48

DIC clinical manifestations

Answer 48

``` Bleeding from multiple sites Thrombotic problems Hypotension and shock Respiratory dysfunction Hepatic and renal dysfunction CNS dysfunciton ```

Question 49

What clinical situations predispose a person to DIC?

Answer 49

Infections (gram- sepsis) Tissue injury (trauma, burn, surgery) Obstetrical complications Certain malignancies