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1

All of procoagulants are synthesized in the liver except?

WV

2

Intrinsic pathway?
1. think which test?
2. Think which factors? 4

Extrinsic?
1. Think which test?
2. Think which factors? 2

1. Intrinsic pathway? Think PTT (partial thromboplastin time)
2. Think VIII, IX, XI, and XII

3. Extrinsic pathway? Think PT
(prothrombin time)
4. Think II and VII

Note: **Both pathways converge on the activation of factor X, which subsequently results in prothrombin activator converting prothrombin into thrombin

3

Which factors are vit K dependant?

Factors VII, X, and prothrombin (Factor II) are vitamin-K dependent and are altered by warfarin (Coumadin) which is why we use the PT-INR to monitor warfarin therapy

4

Antithrombotic Termination
The termination phase of the coagulation process involves two circulating enzyme inhibitors. What are these? 2

1) Antithrombin (formerly called antithrombin III)
2) Tissue factor pathway inhibitor
AND
Clotting-initiated inhibitory process, the protein C pathway

5

Hemostasis Physiology
Antithrombin does what? 2

1. activates coagulation factors and neutralizes thrombin (the last enzyme in the pathway for the conversion of fibrinogen to fibrin)

2. complexes with naturally occurring heparin to accelerate and provide protection against uncontrolled thrombus formation on endothelial surfaces.

6

Hemostasis Physiology
1. What does Protein C do?
2. Protein s?

1. Protein C
A plasma protein
Acts as an anticoagulant protein by inactivating factors V and VIII

2. Protein S
A plasma protein
Breaks down fibrin into fibrin degradation products that act as anticoagulants

7

Fibrinolysis
3 steps

1. Plasminogen binds fibrin and tissue plasminogen activator (tPA)
2. Complex leads to conversion of the proenzyme plasminogen to active, proteolytic plasmin
3. Plasmin cleaves polymerized fibrin strand at multiple sites and releases fibrin degradation products including D-Dimer

8

Bleeding Disorders
1. Defects in Platelet number? 3
2. Defects in Platelet function? 1
3. Defects in the coagulation cascade? 4

1. Defects in Platelet number
-ITP
-Thrombotic Thrombocytopenic Purpura
-Hemolytic-Uremic Sundrome

2. Defects in Platelet function
-Aspirin (drug-induced) platelet dysfunction


3. Defects in the Coagulation Cascade
-Hemophilia A
-Hemophilia B (Christmas Disease)
-von Willebrands Disease
-Vitamin K deficiency

9

1. Normal platelet count?
2. Thrombocytopenia?
3. Milld?
4. Severe?

1. Normal 100,000-400,000 cells/mm
2. less than 100,000 -Thrombocytopenia
3. 50,000-99,999 Mild
4. less than 50,000 Severe

10

Bleeding time normals?

2-8 minutes

11

PARTIAL THROMBOPLASTIN TIME
1. Measures what?
2. Normal value?

1. Measures Effectiveness of the Intrinsic
Pathway



2. NORMAL VALUE
25-40 SECS

12

1. What is thrombin time?
2. Normal?
3. Measure of what?

1. Time for Thrombin To Convert Fibrinogen to Fibrin Monomer


2. NORMAL VALUE
9-13 SECS


3. Measure of Fibrinolytic Pathway

13

Hemostasis is DEPENDENT UPON? 5

1. Vessel Wall Integrity
2. Adequate Numbers of Platelets
3. Proper Functioning Platelets
4. Adequate Levels of Clotting Factors
5. Proper Function of Fibrinolytic Pathway

14

What questions should I ask in the history if I suspect a bleeding abnormality?
4

1. Family History
2. Medications
3. Past Medical History
4. Previous Challenges to Hemostasis

15

Clinical Features of anemia? 5

1. Palpitations
2. Dizziness
3. Orthostatic Hypotension
4. Exertional Intolerance
5. Tinnitus

16

PE for anemia? 5

1. Pale conjunctiva or skin
2. Tachycardia
3. Systolic murmurs
4. Tachypnea at rest and
5. hypotension
are late signs

17

1. Presence of what are diagnostic of anemia? 3
2. Determining the exact etiology of the anemia is not essential in the ED, except in when?
3. Initial eval should include ? 5

4. What are the initial studies needed in patients with suspected bleeding disorders?
3

1.
-decreased RBC count,
-Hemoglobin, and
-Hematocrit

2. the face of acute hemorrhage

3.
-Hemoccult exam,
-CBC,
-retic count,
-Review of RBC indices, and
-smear

4. A
-CBC with platelet count,
-PT and
-PTT

18

Disorders of Secondary Hemostasis
1. These are problems with what?
2. Intrinsic pathway? 3
3. Extrinsic? 1

1. Problem with the coagulation factors themselves

2. Instrinsic Pathway
-Hemophilia A
-Hemophilia B
-vWF
3. Extrinsic Pathway
-Vitamin K deficiency

19

Approach to the thrombocytopenic patient
1. HX? 6
2. assess the number and function of platelets with what? 2

History
1. Is the patient bleeding?
2. Are there symptoms of a secondary illness? (neoplasm, infection, autoimmune disease)
3. Is there a history of medications, alcohol use, or recent transfusion?
4. Are there risk factors for HIV infection?
5. Is there a family history of thrombocytopenia?
6. Do the sites of bleeding suggest a platelet defect?

Assess the number and function of platelets
1. CBC with peripheral smear
2. Bleeding time or platelet aggregation study

20

Clinical manifestations: Hemophilia
(hemophilia A & B are indistinguishable)
Symptoms? 7

1. Hemarthrosis (most common): Fixed joints
2. Soft tissue hematomas (e.g., muscle)
3. Muscle atrophy
4. Shortened tendons
Other sites of bleeding
5. Urinary tract
6. CNS, neck (may be life-threatening)
7. Prolonged bleeding after surgery or dental extractions

21

Hemophilia signs?

1. Swollen, painful joints
2. Local bleeding out of proportion to injury
3. Subcutaneous bleeding
4. Bleeding from mucous membranes
5. Abdominal pain, distension
6. Hematemesis, melena

22

Hemophilias
1. Prolongation of what?
2. Hemophilia A deficiency in?
3. B?

1. Prolongation of the aPTT (the PT will remain normal)

2. Hemophilia A (deficiency in factor VIII)
3. Hemophilia B (deficiency in factor IX) (Christmas Disease)

23

Hemo A etiology?

X-linked recessive pattern of inheritance

24

Describe the PP of Hemophilia A?


What is the kind of bleeding we are really worried about in these pts?

The blood of a person with hemophilia does not clot normally.
He does not bleed more profusely or more quickly than other people; however, he bleeds for a longer time.
External wounds are usually not serious.

Far more important is internal bleeding
These hemorrhages are in joints, especially knees, ankles and elbows; and into tissues and muscles

25

Signs and Symptoms
Hemophila A
? 7

1. Petechiae and ecchymosis are characteristically absent.
2. Bleeding into joints- Knees, ankles, elbows
3. Bleeding into muscles- Spontaneous hemarthoses in severe disease
4. GI bleeding
5. Those with mild disease bleed after major trauma or surgery.
6. Those with moderately severe disease bleed with mild trauma or surgery.
7. Those with severe disease bleed spontaneously.

26

Hemophilia A
Lab findings? 5

1. PTT is prolonged
2. Factor VIII:C is reduced
3. vWF is normal
4. PT, Fibrinogen levels are normal.
5. Diagnosis is confirmed by decreased Factor VIII levels.

27

Hemophilia A
Treatment? 4

1. Avoid ASA
2. Factor VIII replacement: Recombinant Factor VIII concentrate

3. Cryoprecipitate

4. For mild hemophilia
DDAVP

**Can use EACA (Amicar) along with the above

28

Hemophilia B
1. AKA?
2. Caused by?
3. How common?
4. Prolonged what?
5. Dx confirmed by?

1. Also called Christmas disease
2. X-linked bleeding disorder caused by deficiency of Factor IX.
3. Less common than hemophilia A.

4. PTT is prolonged.
5. Diagnosis is confirmed by demonstrating decreased Factor IX levels.

29

Hemophilia B
TX? 2

1. Avoid ASA
2. Factor IX concentrates
Factor VIII concentrates are INEFFECTIVE

30

Von Willebrand’s Disease
1. Etiology?
2. What is it?
3. What is VW required for?
4. Also carries what?

1. Autosomal dominant pattern

2. Disorder of platelet function and coag pathway
-Deficiency of von Willebrand Factor (vWF)

3. vWF is required for adequate platelet adhesion
4. Also a carrier molecule for Factor VIII in the plasma
-Factor VIII is rapidly degraded, limiting its availability for coagulation with vWF deficiency.