Coagulation

Question 1

What does the healing process consist of?

Answer 1

Blood Clotting
Inflammation & the Immune Response
Wound Healing
Termination of Blood Clotting
Clot Lysis
Termination of Inflammatory Response, the Immune Response and Wound Healing

Question 2

What are 4 clotting factors?

Answer 2

Platelets
Soluble Clotting Factors
Tissue Factor
Collagen & Phospholipids

Question 3

What are 5 anti clotting factors?

Answer 3

Nitric oxide (NO)
Protein C & S
Anti-Thrombin III
Fibrinolytics
Prostacyclin

Question 4

What are 3 vessel bound clot inhibitors?

Answer 4

Vascular Endothelial ADPase
Prostacyclin
NO

Question 5

What are 4 vessel bound clot initiators?

Answer 5

Tissue Factor
von Willebrand Factor
Collagen
Thromboxane A2

Question 6

2 tests of clotting ability

Answer 6

protime (PT)

Activated Partial Thromboplastin Time (aPTT)

Question 7

Protime (PT)

Answer 7

Most Sensitively Measures the Concentration of Clotting Factors in the Extrinsic Pathway and the Common Pathway, Many of Which Depend on Vitamin K for their Activity: F II, F VII, F IX, & F X

PT is prolonged when coumadin decreases the vit K factors

Question 8

aPTT

Answer 8

Most Sensitive to the Concentration of Clotting Factors in the Intrinsic Pathway and the Common Pathways: F XI, F IX, F VIII, F X, F II (Prothrombin) & Fibrinogen

Question 9

Von Willebrand Disease

Answer 9

Most Common Inherited Bleeding Disorder; 1% Prevalence in US; Most are Asymptomatic

Question 10

Major Functions of von Willebrand Factor

Answer 10

Binds Factor VIII & Extends Life of F VIII
Binds Platelets to Injured Vessel Endothelium
Helps to Insure that Coagulation & Healing take place at site of Vessel Injury

Question 11

Clinical Presentation of von Willebrand Factor

Answer 11

Mucosal Bleeding including Epistaxis & After Dental Extractions
Post Op Bleeding
Metromenorrhagia

Question 12

Von Willebrand Factor are stored in what?
production stimulated by what?
release is stimulated by what?

Answer 12

Stored in Vessel Endothelial Cells and Platelets
Its Production is Stimulated by Estrogen and T4
Its Release is Stimulated by Vasopressin, Epinephrine, Histamine & Thrombin
Ultra-large Multimers are Broken Down by the Enzyme ADAMTS-13
Too Many Ultra-Large Multimers in the Circulation Will Causes Pathological Clotting: TTP

Question 13

Type 1 Von Willebrand Disease Labs and Treatment

Answer 13

Most Common
Autosomal Co-Dominant
Normal Distribution of Multimers; Decreased Quantity vWF
decreased vWAg, decreased vW F Activity, decreased F VIII Activity
Responds to DDAVP
DDAVP can be given as Nasal Spray or IV

Question 14

Type 2 a, b & m

Von Willebrand Disease

Answer 14

Qualitative Abnormalities in vWF or Abnormal Distribution of Multimers
Type 2b ( excessively big multimers) can be associated with Thrombocytopenia and should NOT Be Treated with DDAVP as this can WORSEN Thrombocytopenia and even precipitate abnormal clotting.

Question 15

Some Tests of Clotting Useful in Diagnosing von Willebrand Disease?

Answer 15

Von Willebrand Factor Antigen
vW Factor Activity
Von Willebrand Factor Multimers
Bleeding Time
Factor VIII Activity

Question 16

Epidemiology of Hemophilia A

Answer 16

X-Linked recessive, therefore severe Sx only in Males
Deficiency of Factor VIII; 1: 5,000 in population
Usually Manifest as Easy Bruising or Bleeding particularly Hemarthoses in Male Toddlers.

Question 17

Hemophilia A Treatment?

Answer 17

Treated with Recombinant Factor VIII Replacement IV as Rx’d by a Hematologist
If Patient born Before 1985 , Hepatitis & HIV were Major Risks
Prophylactic Rx is Desirable
After Prolonged Rx, Inhibitors can Form: A Big Problem
Management Should Strive to Avoid Painful Joint Bleeding & Deformity

Question 18

Hemophilia B:

Answer 18

Deficiency of F IX
X-Linked recessive, therefore severe Sx only in Males
Clinically Identical to Hemophilia A
1: 30,000
Treated with Recombinant Factor IX Concentrate which can be Pro-thrombotic

Question 19

Factor XI Deficiency epidemiology

Answer 19

Autosomal Co-dominant
Family Hx Usually +
Rare in the General Population, but Heterozygotes may be present in as many as 6% of the Jewish Population.
Only few are Sx’ic and most present in Adulthood as Heterozygotes have Mild Sx
Sx Similar to Hemophilia
Usually Rx’d with Fresh Frozen Plasma (FFP)

Question 20

Vitamin K absorbed?

Answer 20

Vitamin K is a fat soluble vitamin absorbed through the gut.

Most of the Vitamin K we absorb is the result of either bacteria in our gut or from plant materials.

Question 21

Vitamin K is important because?

Answer 21

Vitamin K is essential for the Post-translational activation of many proteins, particularly Clotting Factors II ( Prothrombin),VII,IX & X.
Vitamin K also actives the Anti-thrombotic Proteins C & S

Question 22

Coumadin

Answer 22

Coumadin® (warfarin) is a Vitamin K Antagonist that works by Inhibiting Vitamin K Reductase. The Reduced Form of Vitamin K is the Active Form.
Coumadin® is metabolized by enzymes of the Cytochrome Family found in the liver, mostly CYP2C9, which has a variety of genetic variants, e.g. CYP2C92 & CYP2C93.

Question 23

Vitamin K Dependent Clotting Factors

Answer 23

The T1/2 of Factor VII is 4 hours.
The Physiologic Anti-Coagulant Effects of Coumadin® Depend on Lowering Levels of Factor II (Prothrombin) and Factor X.
Therefore when Coumadin is Started one may Falsely Sense the the Patient is Anticoagulated when he is NOT.
Conversely When Coumadin is Stopped, one may Falsely think that the Anti-coagulant Effect of Coumadin is gone, when it is NOT.

Question 24

Coagulopathy of Kidney Disease

Answer 24

More Mild than that of Liver Disease, but Can be Associated with an Increased Tendency for Both Thrombosis and Bleeding.
Restoring Renal Function with Dialysis or Other Measures is Important.
FFP and Sometime Platelet Transfusion are Helpful.

Question 25

Disseminated Intravascular Coagulation (DIC)

Answer 25

Symptom of Other Pathological Process, a Syndrome. The Clinical Hallmark of this Syndrome is Diffuse Bleeding frequently from Mucosal Sites, Sites of Previous Surgery or Instrumentation and Organ Failure d/t Thromboses.

Question 26

The Causes or Clinical Scenarios in Which One Might See DIC

Answer 26

Metabolic Infectious Neoplastic Immune/Inflammatory/ Injury

Question 27

5 Immune/Inflammatory/ Injury that cause DIC

Answer 27

Brain Injury Fat or Amniotic Fluid Embolus Abrutio placentae Severe Pre-eclampsia or HELLP Syndrome ( Hemolysis, Elevate LFTs, & Low Platelets)

Question 28

Labs for DIC

Answer 28

Micro-angiopathic Hemolytic Anemia Thrombocytopenia DIC and TTP can share some Characteristics, BUT in TTP the PT & aPTT should be Normal and FDPs should be Normal or nearly Normal

Question 29

How do you treat DIC

Answer 29

First Treat the Underlying Cause of the DIC! Next Think about Replacing Clotting and Anti-clotting Factors with FFP. Use Platelet Transfusions Sparingly Treatment with Anti-coagulants is Risky

Question 30

Heparin and Other Clotting Factor Inhibitors

Answer 30

Unfractionated Heparin is a sulfated polysaccharide of various Molecular Weights mostly derived from porcine intestine. Heparin Functions by Accelerating the Action of Antithrombin. Antithrombin has its Most Significant Biological Impact by Inhibiting Factor Xa.

Question 31

What is Low Molecular Weight Heparin?

Answer 31

is Synthesized from Unfractionated Heparin. It is dosed based on the Patient’s Weight. No monitoring is Routinely Done; One Can Measure Anti-Xa Activity. Normal Renal Function is Important for the Rx of LMWH. **HIT less likely

Question 32

Unfractionated Heparin Activity is Generally measured how?

Answer 32

Generally Monitored by Measuring the aPTT. Therapeutic: 2 -3 x Normal

Question 33

Fondaparinux is?

Answer 33

synthetic polysaccharide that also binds to Antithrombin and Functions Like Heparin as an Antithrombin Accelerator. only Approved for Deep Venous Thrombosis (DVT) Prophylaxis

Question 34

Dabigatran ( Pradaxa® )

Answer 34

an Oral Direct Thrombin Inhibitor. It is Approved for Prophylaxis of Stroke in Patients with Atrial Fibrillation.

Question 35

Aspirin high doses

Answer 35

Higher Doses Aspirin (ASA) Inhibits both COX 1 & 2, Lowering Levels of the Anti-thrombotic Protein, Prostacyclin as well as Other Inflammatory Proteins.

Question 36

ASA low doses

Answer 36

Anti-thrombotic dose of ASA is 85 -325 mg p.o. Q Day. Since this drug irreversibly binds COX1, it’s effects last for the life of the Platelet, ~ 7 Days. Higher doses are NOT Effective as Anti-platelet Rx

Question 37

Plavix® (clopidogrel)

Answer 37

The Oral Inhibitors of P2Y12 | Indicated for Use with ASA to Lower Risk of Stroke or MI, after coronary stenting or recent MI.

Question 38

GPIIb/IIIa

Answer 38

is an Adhesion Receptor on Surface of Platelets. In its active form it Binds Fibrinogen and vWF. (abciximab) (eptifibatide). Administered Intravenously

Question 39

GPIIb/IIIa indicated in what?

Answer 39

Indicated in Acute MI when patients are Undergoing Coronary Stenting

Question 40

What is the Most Common Inherited Hypercoaguable State is Due to

Answer 40

Factor V Leiden ( VL)

Question 41

Treatment of Factor VL

Answer 41

Asymptomatic Carriers: Education about Increased Risk Situations Patients with Factor VL in High Risk Situations should be Rx’d with Anti-coagulation till that Situation is Resolved Patients with > One Previous DVT or PE: Anticoagulation Probably for Life

Question 42

Prothrombin Gene Mutation G20210A

Answer 42

Second Most Common Inherited Hypercoaguable State Autosomal Co-dominant Results in Increased Plasma Levels of Prothrombin

Question 43

Situational Risk Factors (Transient) for hypercoaguable states

Answer 43

``` HIT Surgery Sepsis Immobilization BCPs or Pregnancy HRT Inflammatory States d/t  Factor VIII ```

Question 44

Acquired Risk Factors (More Permanent) hypercoaguable states

Answer 44

``` Inflammatory Bowel Disease Portal Hypertension Cancer & Cancer Chemotherapy Nephrotic Syndrome Anti-Phospholipid Antibody Syndrome ```

Question 45

Treatment of Antiphospholipid Antibody Syndrome

Answer 45

Routine Rx of Thrombosis with Heparin and Coumadin are Appropriate Monitoring and Proper Dosage may be Difficult as Baseline aPTT and Occasionally PT may be Abnormally Elevated Immuno-suppressive Rx and ASA May have a Role

Question 46

Clotting Problems Can Be Divided Into

Answer 46

Problems of the Vessel Walls (We Did Not Discuss These in Detail) Problems with the Soluble Clotting Factors Problems with The Soluble Anti-clotting Factors Problems with Platelet Discussed Here and in the Thrombocytosis Lecture and the Thrombocytopenia Lecture Problems with a Mixture of the Components of the Clotting System

Question 47

3 Problems of the Vessel Walls

Answer 47

Vessel Injury Atherosclerosis Vessel malformation

Question 48

3 Problems with the Soluble Clotting Factors

Answer 48

Factor Deficiencies: VIII, IX, vWF Factor Inhibitors: anti-Factor VIII Overactive Clotting Factors: VL or Prothrombin Mutation

Question 49

5 Problems with The Soluble Anti-clotting Factors

Answer 49

``` Deficiency of Protein C &S Coumadin Anti-phospholipid Syndrome Augmentation of Anti-Thrombin Heparin ```

Question 50

3 Mixed Coagulopathies

Answer 50

DIC Coagulopathy of Liver Disease Coagulopathy of Kidney Disease