S.p. Exam #1 - Coagulative Disorders

Front 1

Hemostasis

Back 1

Maintenance of clot-free, flowing blood within the vascular system, while also allowing the rapid formation of a solid clot to close ruptures/injury

Front 2

Fibronolysis

Back 2

The dissolution/breaking apart of fibrin clots; a normal component of hemostasis

Front 3

Thrombosis

Back 3

A pathologic process; the formation of a clot within the uninterrupted vascular system; a pathologic extension of hemostasis

Front 4

Diathesis

Back 4

A condition which makes the body tissues react with heightened susceptibility (e.g., bleeding diathesis)

Front 5

Coagulopathy

Back 5

Any disorder of blood coagulation (bleeding or thrombosis)

Front 6

Three Important Contributors of Normal Hemostasis:

Back 6

1) The Vasculature (esp. endothelium)
2) Platelets
3) Coagulation Proteins

Front 7

Development of a Hemostatic Plug: Overview

Back 7

1) Blood Vessel Injury (usu. endothelial)
2) Immediate Vasoconstriction (neurogenic)
3) Platelet Adhesion to Collagen
4) Platelet Activation
5) Coagulation Cascade-Permanent Fibrin/Platelet Clot
6) (Induction of Fibrinolysis)

Front 8

The vascular endothelium....

When Uninjured: _____ Functions
When Injured: _____Functions

Back 8

When Uninjured: Anticoagulant Functions
When Injured: Procoagulant Functions

Front 9

2 proteins secreted by platelets

Back 9

- alpha granule
- dense bodies

Front 10

Platelet Activation

Back 10

Adhesion & Shape Change:
- platelets adhere to nonendothelial injury site 
- (e.g., collagen). vWF, GPIb

Secretion:
- alpha granules and dense bodies released.

Aggregation:
- platelets attach to each other.
- GPIIb/IIIa, fibrinogen

Front 11

Activation and Adhesion step of Platelet Activation

Back 11

- Platelets sitting on the collagen – vWF is there
- Endothelial cells and deposited vWF there  attracts platelets because they have GpIb, which is always on the platelet membrane. It is always there acting like a connection to vWF.
- Lock and key analogy
- vWF also circulates in the blood, but it also gets secreted in the immediate environment of injury.

Front 12

What is critical in all stages of platelet activation?

Back 12

Ca++ critical in all stages of platelet activation; the more Ca++ in platelets, the more activation there is

Front 13

The more vessel injury there is, the (more/less) platelet activation there is

Back 13

MORE

Front 14

Dense bodies and alpha granules --> (initiate/terminate) coagulation cascade and aggregation

Back 14

INITIATE

Front 15

all coagulation factors except vWF are made where?

Back 15

in the liver

Front 16

all coagulation factors, except ___ are made in the liver

Back 16

vWF

Front 17

which factors are Vitamin K dependent?

Back 17

Factors II, VII, IX, and X are Vit K-dependent (2, 7, 9, 10)

Vit K is fat-soluble and absorbed in small intestine

Front 18

intrinsic factors

Back 18

8, 9, 11, 12

Front 19

extrinsic factors

Back 19

7

Front 20

common factors

Back 20

1 (fibrin) ,2 (prothrombrin), 5 , 10,
(small $$$ bills !!!!!)

Front 21

extrinsic vs. intrinsic

Back 21

Extrinsic
- ie: tissue damage like a cut (not just endothelial damage) --> mainly turns on VII
- Tissue factor (produced in endothelium) turns on the coagulation cascade when there is gross damage. It is like the switch that gets turned on and activates factor VII. VII  VIIa (active VII).
Will activate factor X

Intrinsic
- microscopic injury (like atherosclerosis – plaques in BV).
- It is NOT tissue damage.
- It is more endothelial --> turns on --> XII --> XI--> --> IX --> VIII (mediator that brings it to the common pathway). (TENET)

Front 22

Deficiencies of Factors 12, 11, 9 and 8 will prolong the _____

Back 22

Deficiencies of Factors 12, 11, 9 and 8 will prolong the PTT and not the PT

Front 23

Deficiency of Factor VII will prolong the _______

Back 23

Deficiency of Factor VII will prolong the PT but not the PTT

Front 24

Diagnosing Coagulation Disorders

Back 24

- Incidental lab result in a pre-op or medical work-up
- Patient presents with bleeding complaints
- Patient gives a personal or family history of bleeding

Front 25

CBC

Back 25

complete blood count (total count of cells) – platelets are important.

You need the CBC to get a platelet count. You can’t count the platelets by themselves.

Make sure the numbers are normal, not necessarily the functions yet. It just the first step

Front 26

Warfarin affects what factor(s)

Back 26

7 --> prolonged PT (extrinsic)

Front 27

PTT

Back 27

measures intrinsic factors (TENE)

twelve, eleven, nine, eight

Front 28

Thrombocytopenias

Back 28

Thrombocytopenias:
- decreased platelet count & prolonged BT

Deficiencies of Extrinsic Pathway (i.e., VII):
- prolonged PT

Deficiencies of Intrinsic Pathway:
- prolonged PTT

Deficiencies of Common Pathway:
- Prolonged PT and PTT

Front 29

Deficiencies of Extrinsic Pathway

Back 29

Thrombocytopenias:
- decreased platelet count & prolonged BT

Deficiencies of Extrinsic Pathway (i.e., VII):
- prolonged PT

Deficiencies of Intrinsic Pathway:
- prolonged PTT

Deficiencies of Common Pathway:
- Prolonged PT and PTT

Front 30

Deficiencies of Intrinsic Pathway

Back 30

Thrombocytopenias:
- decreased platelet count & prolonged BT

Deficiencies of Extrinsic Pathway (i.e., VII):
- prolonged PT

Deficiencies of Intrinsic Pathway:
- prolonged PTT

Deficiencies of Common Pathway:
- Prolonged PT and PTT

Front 31

Deficiencies of Common Pathway

Back 31

Thrombocytopenias:
- decreased platelet count & prolonged BT

Deficiencies of Extrinsic Pathway (i.e., VII):
- prolonged PT

Deficiencies of Intrinsic Pathway:
- prolonged PTT

Deficiencies of Common Pathway:
- Prolonged PT and PTT

Front 32

Vascular Disorders

Back 32

- Relatively common
- Mostly acquired and often treatable
- Mostly small hemorrhages (petechiae, purpura)
- Coag. Profile: Normal or +/- prolonged BT

Front 33

Vascular Disorders: Acquired Causes

Back 33

- Infectious (esp. meningococcemia, rickettsiae, bacterial endotoxins)
- Drug-Induced Vasculitides
- Collagen-Vascular Diseases (e.g., SLE)
- Age (poor connective tissue, malnutrition)
- Vitamin C Deficiency (scurvy)-rare
- Cushing’s Syndrome (wasting)

Front 34

Vascular Disorders: Hereditary Causes

Back 34

- Ehlers-Danlos Syndrome (connective tissue disorder)
- Henoch-Scholein Purpura (vasculitis)
- Hereditary Hemorrhagic Telangiectasia

Front 35

2 general categories of Platelet Disorders

Back 35

Two General Categories:
Thrombocytopenias (reduced platelet count) AKA quantitative
Thrombocytopathies (defective platelet function) AKA qualitative

Front 36

Thrombocytopenias

Back 36

- Def.: platelet count < 150,000/mm3 (normal = 150,000-450,000)
- Vast majority acquired/iatrogenic
- Signs/symptoms: (small vessel) bleeding from skin, mucous membranes of gingiva, GI, and GU tracts (hematuria)--petechiae, purpura
- Bleeding from surgery or trauma when counts 20-50,000; spontaneous bleeding only if <20,000; increased risk of intracranial bleeds if <10,000
- Coag. Profile: low platelet count, prolonged BT

Front 37

what is normal platelet count?

Back 37

normal = 150,000-450,000

Front 38

what is the platelet count for thrombocytopenias

Back 38

- Def.: platelet count < 150,000/mm3 (normal = 150,000-450,000)
- Vast majority acquired/iatrogenic
- Signs/symptoms: (small vessel) bleeding from skin, mucous membranes of gingiva, GI, and GU tracts (hematuria)--petechiae, purpura
- Bleeding from surgery or trauma when counts 20-50,000; spontaneous bleeding only if <20,000; increased risk of intracranial bleeds if <10,000
- Coag. Profile: low platelet count, prolonged BT

Front 39

signs/symptoms of thrombocytopenias

Back 39

- Def.: platelet count < 150,000/mm3 (normal = 150,000-450,000)
- Vast majority acquired/iatrogenic
- Signs/symptoms: (small vessel) bleeding from skin, mucous membranes of gingiva, GI, and GU tracts (hematuria)--petechiae, purpura
- Bleeding from surgery or trauma when counts 20-50,000; spontaneous bleeding only if <20,000; increased risk of intracranial bleeds if <10,000
- Coag. Profile: low platelet count, prolonged BT

Front 40

causes of thrombocytopenias

Back 40

MOSTLY ACQUIRED !!

Infiltrative bone marrow diseases
(leukemias, metastatic cancers)

Defective platelet production
(aplastic anemia, suppressive drugs/chemotherapeutic agents, alcoholism, B12/folate deficiency, HIV/AIDS)

Increased platelet destruction in blood
(infectious agents, certain drugs, splenomegaly, anti-platelet Ab’s in ITP & AIDS, TTP, prosthetic heart valves, HTN, DIC, atherosclerosis)

“Dilutional thrombocytopenia”
(from massive transfusions)

Rare hereditary diseases

Front 41

Thrombocytopathies

Back 41

- Defective platelets
- Vast majority acquired/iatrogenic
- Similar presentations to patients with thrombocytopenias
- Coag. Profile:
--- Normal platelet count (different from thrombycytopenia)
--- Prolonged BT

Front 42

difference in the coagulation profile between thrombocytopenias and thrombocytopathies

Back 42

thrombocytopenias have DECREASED platelet count and prolonged BT

thrombocytopathies have NORMAL platelet count and prolonged BT

Front 43

Thrombocytopathies: Acquired Causes

Back 43

- **Aspirin (ASA): 1000mg prolongs BT significantly and irreversibly for 10 days!
- NSAID’s (ibuprofen, indomethacin, etc.): effects last only 1-2 days, except ibuprofen, which lasts 10 days as ASA does
- Uremia (end stage renal disease)
- Liver Disease
- Alcoholism

Front 44

difference between aspirin and NSAIDs & ibuprofin

Back 44

- **Aspirin (ASA): 1000mg prolongs BT significantly and irreversibly for 10 days!
- NSAID’s (ibuprofen, indomethacin, etc.): effects last only 1-2 days, except ibuprofen, which lasts 10 days as ASA does

Front 45

1000mg Aspirin prolongs BT significantly and irreversibly for ____days

Back 45

- **Aspirin (ASA): 1000mg prolongs BT significantly and irreversibly for 10 days!
- NSAID’s (ibuprofen, indomethacin, etc.): effects last only 1-2 days, except ibuprofen, which lasts 10 days as ASA does

Front 46

NSAIDs prolong BT significantly and irreversibly for ____days

Back 46

- **Aspirin (ASA): 1000mg prolongs BT significantly and irreversibly for 10 days!
- NSAID’s (ibuprofen, indomethacin, etc.): effects last only 1-2 days, except ibuprofen, which lasts 10 days as ASA does

Front 47

Thrombocytopathies: Hereditary Causes (rare)

Back 47

Bernard-Soulier Syndrome: Aut. rec., GPIb deficiency--adhesion dysfunction

Glanzmann’s Thrombasthenia: Aut. rec., GPIIb/IIIa deficiency--aggregation dysfunction

Storage Pool Disorders: Usually aut. rec., alpha and dense granule deficiencies--secretion dysfunction

Front 48

Bernard-Soulier Syndrome

Back 48

Thrombocytopathies: Hereditary Causes (rare)

Bernard-Soulier Syndrome: Aut. rec., GPIb deficiency--adhesion dysfunction

Glanzmann’s Thrombasthenia: Aut. rec., GPIIb/IIIa deficiency--aggregation dysfunction

Storage Pool Disorders: Usually aut. rec., alpha and dense granule deficiencies--secretion dysfunction

Front 49

Glanzmann’s Thrombasthenia

Back 49

Thrombocytopathies: Hereditary Causes (rare)

Bernard-Soulier Syndrome: Aut. rec., GPIb deficiency--adhesion dysfunction

Glanzmann’s Thrombasthenia: Aut. rec., GPIIb/IIIa deficiency--aggregation dysfunction

Storage Pool Disorders: Usually aut. rec., alpha and dense granule deficiencies--secretion dysfunction

Front 50

Storage Pool Disorders

Back 50

Thrombocytopathies: Hereditary Causes (rare)

Bernard-Soulier Syndrome: Aut. rec., GPIb deficiency--adhesion dysfunction

Glanzmann’s Thrombasthenia: Aut. rec., GPIIb/IIIa deficiency--aggregation dysfunction

Storage Pool Disorders: Usually aut. rec., alpha and dense granule deficiencies--secretion dysfunction

Front 51

Glycoprotein IIb/IIIa

Back 51

integrin complex found on platelets.

It is a receptor for fibrinogen and aids in platelet activation.

The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence

Platelet activation by ADP (blocked by clopidogrel) leads to a conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrin.

Front 52

The Hemophilias (Factor Deficiencies)

Back 52

Vast majority acquired

Presentation: Deep bleeding (e.g., hemarthroses, GI/GU bleeding), ecchymoses (bruises)/hematomas following trauma, prolonged bleeding following a cut or surgery.Petechiae/purpura uncommon

Coag. Profile: (usu.) Normal plt count; prolonged PT &/or PTT

Front 53

Are most cases of the hemophilias acquired or hereditary ?

Back 53

Vast majority acquired

Presentation: Deep bleeding (e.g., hemarthroses, GI/GU bleeding), ecchymoses (bruises)/hematomas following trauma, prolonged bleeding following a cut or surgery.Petechiae/purpura uncommon

Coag. Profile: (usu.) Normal plt count; prolonged PT &/or PTT

Front 54

How would you become hemophilic

Back 54

Acquired:
- very common and important
- Usually multiple factors deficient
- Clinical history critical, as lab results are complex

Hereditary:
+/- family history
- single factor deficiencies

Front 55

Acquired Hemophilias: Major Causes

Back 55

- Vitamin K Deficiency &/or Intestinal Malabsorption
- Liver Disease
- Renal Insufficiency/Failure
- DIC
- Acquired vWD
- Acquired Anti-Factor Antibodies (Inhibitors)

Front 56

Vitamin K Deficiency

Back 56

Deficient factors II, VII, IX, and X (2, 7, 9, 10)

Prolonged PT (and PTT)

Common in malnourishment, alcoholism, gallbladder disease/biliary obstruction, intestinal disease (with malabsorption), neonatal period (esp. preemies and breast-fed neonates)

Treatment: oral/IM/IV Vitamin K

PT/PTT correct (if liver healthy) within days with oral tx, 24hrs with IM tx, and 3hrs with IV tx

Front 57

Liver Disease

Back 57

All coag. factors (except vWF) synthesized in liver; therefore, all potentially affected in severe liver disease (e.g., cirrhosis)

85% of liver disease patients have at least one hemostatic abnormality

15% have clinical bleeding

Vit K-dependent factors affected first!!

Coag. Profile:
prolonged PT early in disease course;
prolonged PTT only with severe disease; (+/- decreased platelet count &/or prolonged BT)

Treatment:
Fresh Frozen Plasma (FFP)-
--> has all factors except XII
Treat underlying liver disease, transplant

Front 58

Fresh Frozen Plasma (FFP

Back 58

Treatment to liver disease

All coag. factors (except vWF) synthesized in liver; therefore, all potentially affected in severe liver disease (e.g., cirrhosis)

85% of liver disease patients have at least one hemostatic abnormality

15% have clinical bleeding

Vit K-dependent factors affected first!!

Coag. Profile:
prolonged PT early in disease course;
prolonged PTT only with severe disease; (+/- decreased platelet count &/or prolonged BT)

Treatment:
Fresh Frozen Plasma (FFP)-
--> has all factors except XII
Treat underlying liver disease, transplant

Front 59

coagulation profile of liver disease

Back 59

All coag. factors (except vWF) synthesized in liver; therefore, all potentially affected in severe liver disease (e.g., cirrhosis)

85% of liver disease patients have at least one hemostatic abnormality

15% have clinical bleeding

Vit K-dependent factors affected first!!

Coag. Profile:
prolonged PT early in disease course;
prolonged PTT only with severe disease; (+/- decreased platelet count &/or prolonged BT)

Treatment:
Fresh Frozen Plasma (FFP)-
--> has all factors except XII
Treat underlying liver disease, transplant

Front 60

Causes of Coagulopathies in Liver Disease

Back 60

Decreased factor production in damaged liver cells (bleeding)

Production of abnormal (nonfunctional) factors (bleeding)

Decreased platelet # or function (bleeding)

Impaired clearance of activated factors (thrombosis)

Front 61

Disseminated Intravascular Coagulation (DIC)

Back 61

Complex, secondary complication to a variety of conditions

Patients usually hospitalized &/or severely debilitated (sepsis, malignancies, shock, severe burns, transfusion reactions, liver disease, **obstetrical complications

Begins as excessive, multifocal thromboses; after a period, platelets and factors consumed, causing life-threatening hemorrhage &/or thromboses (strokes, MI’s, ARF)

Coag. Profile: Prolonged PT and PTT, decreased platelets and fibrinogen, increased fibrin split products

Treatment: Very difficult; double edged sword; treating underlying condition is best approach, but often impossible

Front 62

Coag. Profile: Prolonged PT and PTT, decreased platelets and fibrinogen, increased fibrin split products

Back 62

Disseminated Intravascular Coagulation (DIC)

Complex, secondary complication to a variety of conditions

Patients usually hospitalized &/or severely debilitated (sepsis, malignancies, shock, severe burns, transfusion reactions, liver disease, **obstetrical complications

Begins as excessive, multifocal thromboses; after a period, platelets and factors consumed, causing life-threatening hemorrhage &/or thromboses (strokes, MI’s, ARF)

Coag. Profile: Prolonged PT and PTT, decreased platelets and fibrinogen, increased fibrin split products

Treatment: Very difficult; double edged sword; treating underlying condition is best approach, but often impossible

Front 63

coagulation profile of DIC

Back 63

Complex, secondary complication to a variety of conditions

Patients usually hospitalized &/or severely debilitated (sepsis, malignancies, shock, severe burns, transfusion reactions, liver disease, **obstetrical complications

Begins as excessive, multifocal thromboses; after a period, platelets and factors consumed, causing life-threatening hemorrhage &/or thromboses (strokes, MI’s, ARF)

Coag. Profile: Prolonged PT and PTT, decreased platelets and fibrinogen, increased fibrin split products

Treatment: Very difficult; double edged sword; treating underlying condition is best approach, but often impossible

Front 64

Hereditary Hemophilias

Back 64

- Von Willebrand’s Disease (VWD) (MOST COMMON)
- Hemophilia A
- Hemophilia B (Christmas Disease)
(All other factor deficiencies-exceedingly rare)

Front 65

vWF

Back 65

produced by endothelium, not liver

Platelet adhesion

Front 66

VWD

Back 66

Very common (frequency 1%), but highly variable & often subclinical until a procedure is performed (often dental!)

Most cases autosomal dominant; variable family histories; men and women equally affected

3 types: I-III (mild-severe), III being rare and aut. recessive

Defective platelet adhesion and decreased Factor VIII level/activity

Variable Presentations: Asymptomatic to spontaneous bleeding from mucous membranes, menorrhagia, etc. Usually similar to platelet coagulopathy presentations

Coag. Profile: (variable) +/- prolonged BT; normal plt count; +/- prolonged PTT**Abnormal Ristocetin Test, decreased Factor VIII levels

Diagnosis: often difficult due to variability of disease; must have a high index of suspicion

Treatment: Cryoprecipitate (VWF + VIII) before surgical/dental procedures

Front 67

coag profile of VWD

Back 67

Very common (frequency 1%), but highly variable & often subclinical until a procedure is performed (often dental!)

Most cases autosomal dominant; variable family histories; men and women equally affected

3 types: I-III (mild-severe), III being rare and aut. recessive

Defective platelet adhesion and decreased Factor VIII level/activity

Variable Presentations: Asymptomatic to spontaneous bleeding from mucous membranes, menorrhagia, etc. Usually similar to platelet coagulopathy presentations

Coag. Profile: (variable) +/- prolonged BT; normal plt count; +/- prolonged PTT**Abnormal Ristocetin Test, decreased Factor VIII levels

Diagnosis: often difficult due to variability of disease; must have a high index of suspicion

Treatment: Cryoprecipitate (VWF + VIII) before surgical/dental procedures

Front 68

Coag. Profile: (variable) +/- prolonged BT; normal plt count; +/- prolonged PTT**Abnormal Ristocetin Test, decreased Factor VIII levels

Back 68

VWD

Very common (frequency 1%), but highly variable & often subclinical until a procedure is performed (often dental!)

Most cases autosomal dominant; variable family histories; men and women equally affected

3 types: I-III (mild-severe), III being rare and aut. recessive

Defective platelet adhesion and decreased Factor VIII level/activity

Variable Presentations: Asymptomatic to spontaneous bleeding from mucous membranes, menorrhagia, etc. Usually similar to platelet coagulopathy presentations

Coag. Profile: (variable) +/- prolonged BT; normal plt count; +/- prolonged PTT**Abnormal Ristocetin Test, decreased Factor VIII levels

Diagnosis: often difficult due to variability of disease; must have a high index of suspicion

Treatment: Cryoprecipitate (VWF + VIII) before surgical/dental procedures

Front 69

How do you diagnose VWD?

Back 69

Ristocetin Test – shows that you have decreased vWF
Since factor VIII is deficient you have increased PTT

How do you treat it?
Give cryoprecipitate (combination of vWF + factor VIII)

Front 70

How do you treat VWD?

Back 70

How do you diagnose it?
-Ristocetin Test – shows that you have decreased vWF
-Since factor VIII is deficient you have increased PTT

How do you treat it?
-Give cryoprecipitate (combination of vWF + factor VIII)

Front 71

cryoprecipitate

Back 71

(combination of vWF + factor VIII)

used to treat VWD

Front 72

Hemophilia A

Back 72

Less common than VWD, but the most common hereditary coagulation disorder causing serious (deep) bleeding

Factor VIII deficiency &/or dysfunction

X-linked recessive: Mothers are carriers, passing disease on to their sons (only rare female carriers with symptomatic disease)

Front 73

the most common hereditary coagulation disorder causing serious (deep) bleeding

Back 73

Hemophilia A

Less common than VWD, but the most common hereditary coagulation disorder causing serious (deep) bleeding

Factor VIII deficiency &/or dysfunction

X-linked recessive: Mothers are carriers, passing disease on to their sons (only rare female carriers with symptomatic disease)

Presentation: Deep bleeding, hemarthroses with crippling deformities; petechiae and ecchymoses characteristically absent

30% with no family history (brothers, maternal uncles, etc.); new mutations?

6-50% Factor VIII activity = mild disease
2-5% Factor VIII activity = moderate ds<
2% Factor VIII activity = severe ds

Coag Profile: Normal platelet count; Prolonged PTT; decreased Factor VIII assay or activity

Treatment: Frequent cryoprecipitate or **Factor VIII concentrate (recombinant lowest risk of disease transmission)

Complications: Crippling joint deformities, AIDS, hepatitis, hemochromatosis, life-threatening hemorrhages

Front 74

presentation of Hemophilia A

Back 74

Less common than VWD, but the most common hereditary coagulation disorder causing serious (deep) bleeding

Factor VIII deficiency &/or dysfunction

X-linked recessive: Mothers are carriers, passing disease on to their sons (only rare female carriers with symptomatic disease)

Presentation: Deep bleeding, hemarthroses with crippling deformities; petechiae and ecchymoses characteristically absent

30% with no family history (brothers, maternal uncles, etc.); new mutations?

6-50% Factor VIII activity = mild disease
2-5% Factor VIII activity = moderate ds<
2% Factor VIII activity = severe ds

Coag Profile: Normal platelet count; Prolonged PTT; decreased Factor VIII assay or activity

Treatment: Frequent cryoprecipitate or **Factor VIII concentrate (recombinant lowest risk of disease transmission)

Complications: Crippling joint deformities, AIDS, hepatitis, hemochromatosis, life-threatening hemorrhages

Front 75

coagulation profile of Hemophilia A

Back 75

Less common than VWD, but the most common hereditary coagulation disorder causing serious (deep) bleeding

Factor VIII deficiency &/or dysfunction

X-linked recessive: Mothers are carriers, passing disease on to their sons (only rare female carriers with symptomatic disease)

Front 76

Coag Profile: Normal platelet count; Prolonged PTT; decreased Factor VIII assay or activity

Back 76

Hemophilia A

Less common than VWD, but the most common hereditary coagulation disorder causing serious (deep) bleeding

Factor VIII deficiency &/or dysfunction

X-linked recessive: Mothers are carriers, passing disease on to their sons (only rare female carriers with symptomatic disease)

Presentation: Deep bleeding, hemarthroses with crippling deformities; petechiae and ecchymoses characteristically absent

30% with no family history (brothers, maternal uncles, etc.); new mutations?

6-50% Factor VIII activity = mild disease
2-5% Factor VIII activity = moderate ds<
2% Factor VIII activity = severe ds

Coag Profile: Normal platelet count; Prolonged PTT; decreased Factor VIII assay or activity

Treatment: Frequent cryoprecipitate or **Factor VIII concentrate (recombinant lowest risk of disease transmission)

Complications: Crippling joint deformities, AIDS, hepatitis, hemochromatosis, life-threatening hemorrhages

Front 77

Hemophilia B (Christmas Disease)

Back 77

- X-linked recessive (mother to sons)
- Factor IX deficiency or dysfunction
- Clinically indistinguishable from Hemophilia A

Presentation: Depends on Factor IX level/activity; from asymptomatic to deep bleeding/hemarthroses

Coag. Profile: Normal plt count; prolonged PTT & reduced Factor IX assay/activity

Treatment: Factor IX concentrate

Front 78

Thrombotic Disorders: Causes

Back 78

- Hematologic Abnormalities: Excessive platelet production (e.g., essential thrombocytosis), RBC production (p. vera, COPD), or WBC production (leukemias)
- Malignancies (hypercoagulability, DIC)
- Multiple Myeloma (increased protein in circulation)
- Oral Contraceptives, Pregnancy
- Smoking, Atherosclerosis
- Prosthetic Heart Valves
- Post-operative Periods (immobilization and increased platelets)
- (Rare) Hereditary Deficiencies of Natural Coagulation Inhibitors