MHD - Lec#2 - Abnormal Hemostasis I & II Flashcards Preview

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Flashcards in MHD - Lec#2 - Abnormal Hemostasis I & II Deck (35):

Alterations in bone marrow results in an increased or decreased platelet count?

What are the following examples of:

- May Hegglin anomaly (autosomal dominant),

Wiskott-Aldrich syndrome,

absent radius syndrome, Fanconi’s anemia


- Marrow hypoplasia, aplasia, replacement by neoplastic cells, marrow fibrosis, radiation injury, leukemia, paroxysmal nocturnal hemoglobinuria (PNH).

2. Hereditary thrombocytopenia


What is a normal platelet count?

200-500 thousand mm3


What is an example of acquired abnormal hematopoiesis?

What drugs often induce thrombocytopenia?

How does hemodialysis affect the number of platelets?

B12/Folate deficiency, pre-leukemia*

- Heparin, gold, quinine, quinidine, sulfonamides, GP IIb/IIIa Inhibitors

= thrombocytopenia


What is the main mechanism of Heparin induced thrombocytopenia?

1. Heprin forms a complex with PF-4
2. Antibodies form against this complex and decrease the number of platelets

- PF-4 comes from LIGHT GRANULES (alpha)


What is ITP?

What is TTP?

ITP: Immune thrombocytopenic purpura
- IgG antibodies made to GpIIb/IIIa
= IMMUNE response

TTP: thrombotic thrombocytopenic purpura
- abnormal vwf multimers which cause arterial thrombi in micro vessels
- result in organ failure etc..


State the following for
Glanzmann's thrombasthenia

1. dominant/recessive/sex or autosomal
2. Which receptor is defective
3. Activation, adhesion, or aggregation defect
4. Bleeding time change or not

Glanzmann’s thrombasthenia

Autosomal recessive,
GPIIb/IIIa defect,
aggregation defect (decreased) ,
bleeding time increased


State the following for
Bernard- Soulier Disease

1. dominant/recessive/sex or autosomal
2. Which receptor is defective
3. Activation, adhesion, or aggregation defect
4. Bleeding time change or not

Autosomal recessive,
GP Ib defect,
adhesion defect* (not aggregation)
bleeding time increased


What is a storage pool disease?

What is polycethemia vera?

decrease dense granule content (ADP, serotonin, histamine, Ca)

no aggregation

2. Acquired disorder of platelets
- cancer of RBCs which hematocrit increases tremendously


What is normal in vascular disorders that are NON THROMBOCYTOPENIA purpuras?

Platelet function and coagulation are normal.

- Easy bruising, bleeding from mucosa, purpura, vasculitis.


What are the following examples of:

1. Ehler Danlos Syndrome (Hypermobile joints. Hyperflexible skin, osteogenesis imperfecta, drugs, infections, amyloidosis)

2. Purpura simplex, amyloids, drugs, steroid purpura (prednisone), Cushing’s syndrome (steroid excess), Henoch-Schonlin purpura (usually drug induced).

= ehler danlos

2. Acquired SUBENDOTHELIAL disorder


What is the most common congenital endothelial disorder ?

What are examples of acquired endothelial disorders?

Hereditary hemorrhagic Telangiectasia (HHT)

Inflammation, vasculitis (drugs, viruses, Rickettsia)


The following are examples of what?

- Orthostatic purpura
- Mechanical purpura (mechanical pressure)
- Increased transluminal pressure

What is a nutritional disorder of the vasculature?

Mechanical disorder

2. Scurvy (vit C deficient)


What occurs in Factor V leiden (aka APC - activated protein C deficiency)?

What is the function of protein C?

Protein C cannot digest and inactivate Factor 5

- cofactor in final pathway activating 10 to 10a & 2 to 2a

- point mutation results in enhanced 5 activity and no inactivation by protein Ca

-protein C and S are anti-coagulant and vitamin K dependent and are carboxylated by gamma-carboxyl glutamic acid

**If activated protein C cannot regulate factor 5 then the coagulation cascade is not controlled and THROMBOSIS occurs!

PROTEIN C - digests factor 5 & 8


What is released by heparin and capable of inhibiting TF and the TF/Factor 7 complex?

tissue Factor Pathway Inhibitor!

- Intrinsic pathway: PTT, heparin, hemophilia

Extrinsic: PT, warfarin/coumadin


What are the most common coagulation defects in the intrinsic pathway?

Hemophilia A (Factor VIII)

Hemophilia B (Factor IX) -9


What factors are involved in 12 to 12a conversion?

Fischer Factor & Fletcher factor (kallikrein)

- Kallikrein can act on HMWK collagen and release KININS

= the most potent vasodilating mechanisms
which is why some patients with coagulation (DIC) will also have hypotension due to decreased BP as a result of kallikrein conversion


PT & warfarin/coumadin are most part of which pathway?



What stabilizes fibrin and leads to cross-linking?

Factor 13 a transamidase


What are the vitamin K dependent proteins?

2,7,9,10 C & S

- Protein C and Protein S
vitamin K dependent proteins just like 2,7,9,10
protein C and S have anti-coagulant function
protein C to Ca by thrombin-thrombomodulin
protein S is a REQUIRED COFACTOR for the transformation of protein C to Ca


What substances are measured by PT?

APTT? and fibrinogen


( all except 7, 13 and protein C and S)


State the following for Hemophilia A & B:

1. Transmission
3. Platelet count

1. sex linked recessive


3. No effect on platelet number


How are Type 1 and 3 vWf diseases different from type 2?

Describe vwf disease.

1 & 3 = decrease in circulating level of factor

2 = QUALITATIVE defect in the protein

= cementing protein made by the endothelium and able to bind vWF to collagen in subendothelium and then to paltelets GpIb  if this binding doesn’t occur there is NO adhesion (lack of first step of coagulation)

Qualitative defect - protein is not binding

Quantitative defect - less production


How would you distinguish hemophilias vs. Von willebrand's disease using the following?

2. Platelet
3. Bleeding time

APTT prolongation
(45s, normal is 30s)
Platelet function-normal
Bleeding time - no effect

Von Willebrand’s Disease
- APTT slightly elevated due to mild reduction in factor VIIIc (almost no change)
- Hemostatic function impaired due to impaired adhesion of platelets to collagen in-vivo. (PLATELETS)
- Bleeding time ELEVATED!!!.


TPP is due to a defect in what enzyme?


Pathogenicity of TPP:
overexpression of VWF multimers trapping platelets and causing occlusion of small vessels = MICROANGIOPATHIC occlusion
ADAMS13 enzyme is deficient and cannot cut down the VWF into small monomers!!!
bleeding due to deficiency of vWF


A decrease in the fibrinogen concentration and an increase in degradation product formation contribute to what?


- Excessive activation of the fibrinolytic system can cause bleeding.


How is primary fibrinolysis different from secondary?

What causes each?


- fibrinogen is converted into FDP only by plasmin (fibrinogen degradation products)

Ex: Dead Baby Syndrome ( Abruptio Placenta)
- snake bite

Overdosage of thrombolytic agents can result in a primary fibrinolytic state and cause bleeding

Secondary: DIC
- both fibrin & fibrinogen are digested by plasmin
(create Fibrinogen DP and Fibrin DP)
- Secondary fibrinolysis is also associated with digestion of clotting factors and consumption of platelets.
***D- Dimer is a hallmark for diagnosis of DIC
usually due to SEPSIS


What is the hallmark of DIC?

D- dimer formation


Deficiency of a2-antiplasmin results in what?

Results in increased fibrinolysis (Bleeding)

anti-plasmin is an inhibitor of plasmin (fibrinolytic enzyme)

- Plasmin is a SERINE PROTEASE
alpha 2 antiplasmin complex will form inactivating PLASMIN

to measure this complex use ELISA method to find out the amount of the complex and the extent of fibronolysis in the patient


How does heparin induced thrombocytopenia occur?

How can drug induced bleeding by heparin be controlled?

1. PF-4 forms a complex with heparin, antibodies attack the complex and degrade it
- thrombocytopenia

2. Heparin Protamine Sulfate!


How are bleeding disorders diagnosed?

1. Bleeding time
2. Platelet count
3. platelet function
Aggregation * (most used)

- Aspirin treated patients will not respond to Arachinodic Acid (inhibits COX2)
test over-ingestion with arachinodic acid aggregation

Collagen can also activate platelets by binding to vWF and GpIb
- collagen induced aggregation is also used


How are the following Thrombophilias diagnosed?

1. Factor V leidein
2. prothrombin 20210
3. Hyperhomocysteinemia

1. Factor V Leiden (APC resistance)
- PCR method to see if a patient is Factor 5 deficient
- 30% of patients who develop DVT

2. Prothrombin 20210
- overproduction of pro-thrombin resulting in thrombosis
- measure with PCR

3. Hyperhomocysteinemia
- homocystein was usually measured in urine, but this defect is due to a methionine transformation meth-THF reductase enzyme is responsible for the transformation and is defective

- test for MTHFR

(methotrexate inhibits MTHFR - used in tx of leukemia and lymphomas)
- some patients develop excessive thrombosis due to inhibition of MTHFR


______ can be increased in diabetes, cancer, inflammation

What is the normal fibrinogen level?

What is the D-dimer test used to diagnose?

1. Plasminogen activator inhibitor (PAI)

Most basic tests are PT, PTT, fibrinogen level, platelet count, and then PCR for molecular diagnosis

2. Fibrinogen normally 400ml/dl

DIC= 200 or 100 ml/dl

3. D - dimer used to diagnose DIC


Which of the blood clotting tests is commonly used for the diagnosis of Hemophilias?

Activated partial thromboplastin time
Prothrombin time/INR
Thrombin time
Bleeding time
Fibrinogen levels

- slight increase of 3-5 seconds

Which is used to monitor Heparin = APTT

Which of blood clotting test is used for monitoring of WARFARIN = PT /INR


A patient was admitted to the hospital with a urinary tract infection. Two days later he developed fever and his coagulation parameters and platelet count became abnormal. Additional test showed D-dimer positive and positive blood cultures for E. Coli. What is the likely diagnosis of this patient

Hypercoaguable state
APC Resistance
Von Willebrand disease



1. Splenectomy results in thrombocytopenia or thrombocytosis?

2. NSAIDS & Aspirin results in quantitative or qualitative changes in platelets?


- platelets are functioning normally and released into circulation

2. QUALITATIVE changes
- function is impaired