Coagulation Disorders

Front 1

Coagulation disorders can result from:
1.
2.
3.
4.

Back 1

1. Decreased number of platelets
2. Decreased function of platelets
3. Coagulation factors deficiency
4. Enhanced fibrinolytic activity

Front 2

What are the 3 groups of coagulation factors?

Back 2

1. Vitamin K dependent
2. Contact activation factors
3. Thrombin sensitive

Front 3

What are the vitamin K dependent factors?

Back 3

II, VII, IX, X

Front 4

What are the contact activation factors?

Back 4

XI, XII, prekallikrein, high-molecular weight kininogen

Front 5

What are the thrombin sensitive factors?

Back 5

V, VIII, XIII and fibrinogen

Front 6

What is circulating in the body as INACTIVE precursors to coagulation factors?

Back 6

zymogens

Front 7

Coagulation is a result of:

Back 7

cascading series of proteolytic reactions

Front 8

What coagulation factors have the longest half-life?

Back 8

I Fibrinogen (100-150 h)

XIII Fibrin stabilizing factor (150h)

Front 9

What coagulation factor has the shortest half-life?

Back 9

VII Proconvertin (4-6h)

Front 10

What 3 pathways are included in the traditional coagulation cascade?

Back 10

1. Intrinsic
2. Extrinsic
3. Common

Front 11

INTRINSIC pathway is initiated when circulating factor ___ comes in contact with __________ membrane.

Back 11

XII; subendothelial

Front 12

EXTRINSIC pathway is initiated by exposure of tissue factor to ______.

Back 12

trauma

Front 13

COMMON pathway is formed when ________ and _______ pathways converge at activation of factor __.

Back 13

intrinsic; extrinsic; X

Front 14

True or False: The TRADITIONAL factor pathway shows interactions with platelets and endothelium.

Back 14

FALSE - does NOT show interactions between platelets and endothelium

Front 15

The traditional pathway is _____ based also known as _______ _______ pathway.

Back 15

cell; tissue factors

(shows platelets and endothelium interactions)

Front 16

Tissue factor is a ________ protein found in:

Back 16

membrane; organs and surrounding vasculature

Front 17

Tissue factor exposed to blood as a consequence of:
1.
2.

Back 17

1. Vessel wall damage
2. Inflammatory cytokine release

Front 18

Coagulation is initiated when factor ____ binds to exposed or expressed ______ ______.

Back 18

VIIa; tissue factor

Front 19

Factor VIIa-tissue factor complex activates factors __ and __.

Back 19

IX and X

Front 20

Activated platelets form complex with factor ___-factor ___ (tenase) and factor ___-factor ___ (prothrombinase)

Back 20

factor IXa-factor VIIIa (tenase); factor Xa-factor Va (prothrombinase)

Front 21

Tenase activates what?

Back 21

factor X

Front 22

Prothrombinase converts __________ to _______.

Back 22

prothrombin to thrombin

Front 23

Thrombin:
1. Activates ________ and catalyzes conversion of ________ to ______
2. Amplifies _________ by activating factors __, ___ & __.

Back 23

1. Activates platelets and catalyzes conversion of fibrinogen to fibrin.
2. Amplifies coagulation by activating factors V, VIII & IX.

Front 24

Factor __ always has to be cleaved to be active.

Back 24

X

Front 25

Maintenance of blood flow includes 4 major components:
1.
2.
3.
4.

Back 25

1. vessel wall
2. platelets
3. coagulation system
4. fibrinolytic system

Front 26

Main factors in homeostasis:
1.
2.

Back 26

1. blood vessel wall
2. activated platelets

Front 27

Vessel wall initiates ___________ and exposure of _________ and _______ factor to blood.

Back 27

vasoconstriction; collagen; tissue

Front 28

Platelets function in response to vascular injury include:

Back 28

adhesion, secretion, aggregation, and elaboration of procoagulant activity

Front 29

Fibrin clot formation is regulated by what?

Back 29

coagulation system

Front 30

Polymerized clot is dissolved by what?

Back 30

fibrinolytic system

Front 31

Plasminogen is primary compound of what? Released in response to what? Converted to what in presence of fibrin? Plasmin digests what?

Back 31

Plasminogen is a primary compound of fibrinolytic system

Released in response to thrombin, venous stasis, physical exercise and ischemia

Plasminogen converted to plasmin in the presence of fibrin

Plasmin digests fibrin, dissolves clots and releases fibrin degradation products (FDPs)

Front 32

What is assessed by Bleeding Time and what can prolong it?

Back 32

Assesses platelet and capillary function and reflects time to cessation of bleeding following standard skin cut

Can be prolonged due to:
1. incorrect performance of test
2. thrombocytopenia
3. platelet dysfunction

Front 33

What does Prothrombin Time (PT) assess and how is it expressed?

Back 33

Assesses activity of vitamin-K dependent proteins (II, VII, IX, X and proteins C and S) and common pathway proteins (factors V and X)

Expressed as INR

Front 34

What are the vitamin-K dependent proteins?

Back 34

II, VII, IX, X and proteins C and S

Front 35

What are the vitamin-K dependent common pathway proteins?

Back 35

factors V and X

Front 36

What is measured by Activated Partial Thromboplastin Time (aPTT) and what can it monitor?

Back 36

Measures activity of intrinsic system and common pathway factors II, V, VIII, IX, X, XI and XII, kininogen, prekallikrein and fibrinogen

Used to monitor heparin therapy

Front 37

What does Thrombin Time measure? What affects this? What does it monitor?

Back 37

Measures conversion of fibrinogen to fibrin

Affected by:
-quantitative and qualitative abnormalities of fibrinogen
-presence of thrombin indicators
-fibrinogen degradation products

Used to monitor systemic fibrinolytic therapy and can be modified for monitoring herparin therapy

Front 38

Hemophilia is a bleeding disorder and a ________ deficiency in _______ _______ ______.

Back 38

congenital; plasma coagulation protein

Front 39

2 types of hemophilia:
1.
2.

Back 39

1. Hemophilia A (classic)
2. Hemophilia B (Christmas disease)

Front 40

Which type of hemophilia is more common?

Back 40

Hemophilia A
(1 in 5,000 male births)

Front 41

Hemophilia A is a deficiency in what?

Back 41

factor VIII

Front 42

Hemophilia B is a deficiency in what?

Back 42

factor IX

Front 43

True or False: Hemophilia is dominant X-linked.

Back 43

FALSE: recessive X-linked

Front 44

True or False: Hemophilia affects both males and females.

Back 44

FALSE - only males (females are carriers)

Front 45

What are some bleeding manifestations associated with hemophilia?

Back 45

-palpable ecchymoses
-bleeding into joint spaces (hemathroses)
-muscle hemorrhages
-excessive bleeding after surgery or trauma

Front 46

The severity of bleeding hemophilia is associated with what?

Back 46

the degree of factors VIII or IX deficiency

Front 47

Who should be considered for hemophilia testing?

Back 47

Males with unusual bleeding, brothers of patients with hemophilia and sisters for carrier testing

Front 48

What are the laboratory tests associated with hemophilia diagnosis?
1. Prolonged?
2. Decreased?
3. Normal (3 things)?

Back 48

1. Prolonged aPTT
2. Decreased factor VIII or factor IX
3. Normal platelet count, von Willebrand factor antigen and activity and bleeding time

Front 49

What are the 4 treatment options for hemophilia?

Back 49

1. recombinant factor VIII
2. plasma-derived products
3. factor VIII concentrate replacement
4. desmopressin

Front 50

Recombinant factor VIII (tmt for Hemophilia A):
1. produced by?
2. derived from?
3. transfected with?

Back 50

1. produced by recombinant DNA technology
2. derived from cultured Chinese ovary or baby hamster kidney cells
3. transfected with human factor VIII

Front 51

True or False: Clinical trials demonstrated that factor VIII products are comparable in effectiveness to plasma-derived products.

Back 51

TRUE.

Front 52

Plasma-derived products (tmt for Hemophilia A):
1. Derived from?
2. Can transmit?
3. More risk for?

Back 52

1. derived from plasma of donors
2. can transmit infection
(need to perform donor screening, test plasma polls for viral infection and viral reduction through purification steps and perform viral inactivation)
3. more risk for patient infection
(cases of hepatitis C have been reported)

Front 53

Factor VIII Concentrate Replacement (Hem A tmt)
1. Dosing depends on?
2. Tmt influenced by?

Back 53

1. Dosing depends on t1/2 of infused factor
2. Tmt influenced by presence or absence of an inhibitory antibody to factor VIII

Front 54

Factor VIII (units) =

Back 54

(desired level - baseline level) x 0.5 x (weight in kg)

Front 55

Desmopressin (Hem A tmt):
1. Adequate for?
2. Synthetic analog of?
3. Can be administered?
4. Side effects?

Back 55

1. Adequate for minor bleeding episodes and minor hem A
2. Synthetic analog of antidiuretic hormone vasopressin
(causes release of von Willebrand factor and factor VIII form endogenous storage sites)
3. can be administered intranasally via concentrated nasal spray
4. side effects: facial flushing, mild HA, increased heart rate and decreased blood pressure

Front 56

What are the 3 treatments for Hemophilia B?

Back 56

1. recombinant factor IX
2. plasma-derived factor IX products
3. factor IX concentrate replacement

Front 57

Recombinant factor IX (tmt for Hem B)
1. Produced in?
2. Products NOT used to produce?

Back 57

1. produced in Chinese hamster ovary cells transfected with factor IX gene
2. blood and plasma products NOT used to produce (excellent viral safety)

Front 58

Plasma-derived factor IX (tmt for Hem B)
1. Derived from?
2. Must perform?
3. Prior to high-purity products prothrombin complex concentrates (PCC) with vitamin-K dependent proteins (II, VII, & X)....?

Back 58

1. derived from plasma (biochemical purification and monoclonal immunoaffinity techniques)
2. must perform viral inactivation measures (solvent detergent or chemical tmt)
3. contained activated factors and were associated with thrombotic complications (DVT, PE, MI, and DIC)

Front 59

Factor IX Concentrate Replacement (Hem B tmt)
1. Factor IX (what type of protein)?
2. Found where?
3. Vd (relationship to factor VIII)?
4. Each unit of factor IX infused per kg body weight increases plasma level by how much?

Back 59

1. small protein
2. in intravascular and extravascular space
3. Vd twice that of factor VIII
4. increases plasma level of factor IX by 1%

Front 60

Plasma-derived factor IX (units) =

Back 60

(desired level - baseline level) x weight in kg

Front 61

What is the effect of prophylactic replacement therapy in hemophilia?

Back 61

-prevents joint bleeding episodes (can decrease joint damage and severe physical disability)
-converts severe hemophilia to milder form

Front 62

What are treatment inhibitors in hemophilia?

Back 62

Neutralizing antibodies to factor VIII and IX develop in a subset of patients

Front 63

Neutralizing antibodies to factor VIII (tmt inhibitor in hemophila):
1. serious complication of?
2. mostly develop in?
3. more common patients with?
4. inhibitors usually immunoglobulins of what subclass?
5. therapy?

Back 63

1. serious complication of factor replacement
2. most inhibitors develop in childhood
3. more common in patients with severe disease
4. inhibitors are usually immunoglobulins of G subclass
5. therapy: treatment of acute bleeding episodes and eradicating inhibitors, supportive measures (immobilization and antifibrinolytics)

Front 64

Von Willebrand Disease:
1. What type of disorder?
2. Prevalence?
3. What type of defect?
4. Type of inheritance?

Back 64

1. Common congenital bleeding disorder
2. Prevalence 1-2%
3. Quantitative and/or qualitative defect of von Willebrand factor
4. Autosomal inheritance (equal frequency in males/females)

Front 65

Von Willebrand factor
1. Type of protein? Involved in?
2. Gene located where?
3. What produces a large primary product?

Back 65

1. Glycoprotein involved in platelet aggregation and coagulation
2. Gene for von Willebrand factor located on chromosome 12
3. Transcription and translation produce a large primary product
-undergoes complex modification resulting in von Willebrand factor multimers

Front 66

Classification of von Willebrand disease:
1. Type of disorder?
2. 3 major subtypes?
3. Tmt options based on?

Back 66

1. heterogenous group of disorders
2. 3 major subtypes:
-types 1 and 3 -> quantitative defects in von Willebrand factor
-type 2 -> functional abnormalities in von Willebrand factor
3. Treatment options depend on subtype

Front 67

Clinical presentation of Von Willebrand Disease:
1. Symptomatic or asymptomatic?
2. Type of bleeding?
3. Bruises?
4. Post-op?

Back 67

1. Asymptomatic
2. Mucocutaneous bleeding
-epistaxis, gingival bleeding, menorrhagia
3. Easy bruising
4. Post-op bleeding

Front 68

Tmt for Von Willebrand Disease depends on?

Back 68

1. type of von Willebrand disease
2. location and severity of bleeding

Front 69

Local measures for tmt of superficial bleeding in von Willebrand disease?

Back 69

ice, topical thrombin

Front 70

In von Willebrand disease, systemic treatment for?

Back 70

bleeding that cannot be controlled with local measures, prevention of bleeding with surgery

Front 71

When is replacement therapy used in von Willebrand disease?
1.
2.
3.

Back 71

1. types 2B, 2M, and 3
2. for type 1 or 2A unresponsive to desmopressin
3. some virus-inactivated, intermediate or high-purity factor VIII concentrates contain sufficient amounts of von Willebrand factor

Front 72

What is a complication of replacement therapy in von Willebrand disease?

Back 72

transmission of blood-borne viruses such as hepatitis and HIV (must screen)

Front 73

Desmopressin (tmt for von Willebrand disease)
1. Stimulates endothelial cell release of?
2. Effective for patients who?
-MOST patients with?
-SOME patients with?
-NOT for?

Back 73

1. stimulates endothelial cell release of von Willebrand factor and factor VIII
2. Effective for patients who have adequate endogenous stores of functional von Willebrand factor
-MOST patients with type 1 disease
-SOME patients with type 2A disease
-NOT recommended for tmt of type 2B (causes release of additional abnormal von Willebrand factor -> thrombocytopenia)

Front 74

Disseminated Intravascular Coagulopathy (DIC):
1. Systemic activation of?
-leads to?
-often compensatory bleeding due to?
2. Same or different causes of DIC?

Back 74

1. Systemic activation of coagulation
-leads to clot formation in microvasculature
-often compensatory bleeding due to biodegradation of coagulation factors and platelets
2. Different causes of DIC

Front 75

Underlying diseases associated with DIC:
1.
2.
3.
4.
5.
6.
7.

Back 75

1. cardiovascular (acute MI, aortic anuerysm)
2. infectious
3. intravascular hemolysis
4. newborn
5. obstetrics
6. pulmonary
7. tissue injury

Front 76

Signs and symptoms of DIC:
1.
2.
3.

Back 76

1. bleeding, thrombosis or both
2. patechiae and purpura
3. hemorrhagic bulae

Front 77

Lab tests for DIC:
1. Elevated/increased (3 things)?
2. Decreased (3 things)?
3. Evidence of?
4.

Back 77

1. Elevated D-dimer, fibropeptides A and B, and prothrombin fragments 1 and 2
2. Decreased antithrombin, fibrinogen, proteins C and S
3. Evidence of end-organ dysfunction or failure
4. Thrombocytopenia

Front 78

DIC
1. If left untreated can lead to?
2. Controversy regarding?
3. Most important?

Back 78

1. If left untreated can lead to hemorrhage and/or thrombosis -> death
2. Controversy regarding optimal treatment
3. Most important -> treat underlying disease

Front 79

True or False: Efficacy of fresh frozen plasma or platelet transfusions in treating DIC has NOT been proven in randomized controlled trials.

Back 79

TRUE
-rational for patients who are bleeding or require invasive procedures
-fresh-frozen plasma replaces clotting factors, fibrinogen, protein S, protein C, antithrombin

Front 80

Anticoagulation as tmt for DIC:
1. Controversial?
2. Heparin interferes with?
-can prevent?
-no effect on?
-shows reduction in morbidity or mortality?
-given how?
3. Contraindicated in?
4. May be good for which patients?

Back 80

1. yes- controversial
2. heparin interferes with thrombin activity
-can prevent future thrombosis
-no effect on established microthrombus in vasculature
-no reduction in morbidity or mortality
-given subq or continuous IV
3. Contraindicated in patients with life-threatening or serious bleeding
4. Patients with symptomatic thromboemboli, fibrin deposition, solid tumors or chronic DIC may benefit from heparin
-start wtih continuous IV hep
-convert to subq when asymptomatic

Front 81

Critically ill patients with DIC may develop?

Back 81

Vitamin K deficiency - require supplement

Front 82

Vitamin K:
1. Fat or water soluble?
2. Cofactor for activation of factors?
3. Necessary for active forms of?

Back 82

1. Fat-soluble vitamin
2. Cofactor for activation of factors II, VII, IX, and X
-required for gamma-carboxylation
-without vitamin K cannot bind Ca or bind to negatively charged phospholipid membranes
3. Necessary for active forms of proteins C and S (inhibits factor Va and VIIIa)

Front 83

Vitamin K deficiency leads to?
-deficiency in factors?
-causes what disease in newborns?
-effects absorption how?

Back 83

Vitamin K deficiency leads to bleeding
-deficiency in factors II, VII, IX, and X
-hemorrhagic disease in newborns
-malabsorption - absorption depends on bile acids and pancreatic enzymes

Front 84

Treatment of Vitamin K deficiency
1.___________
-dose, frequency and duration depends on?
-can be given?
-PO administration causes?
-route of admin depends on?

2. _________________
-for life-threatening bleeding
-

Back 84

1. Phytonadione
-dose, frequency and duration depends on severity of deficiency
-can be given PO, IM, SubQ, or IV
-PO admin causes faster coagulation (6-12 hrs) than parenteral (12-24 hrs)
-route of admin depends on severity and cause of vitamin K deficiency (avoid IM in severe hypoprothrombinemia)


2. Fresh frozen plasma for life-threatening bleeding