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PHARM/MHD - Exam #4 > MHD - Lec#2 - Abnormal Hemostasis I & II > Flashcards

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

1
Q

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

A

Decreased

  • Marrow hypoplasia, aplasia, replacement by neoplastic cells, marrow fibrosis, radiation injury, leukemia, paroxysmal nocturnal hemoglobinuria (PNH).
    2. Hereditary thrombocytopenia
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2
Q

What is a normal platelet count?

A

200-500 thousand mm3

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3
Q

What is an example of acquired abnormal hematopoiesis?

What drugs often induce thrombocytopenia?

How does hemodialysis affect the number of platelets?

A

B12/Folate deficiency, pre-leukemia*

  • Heparin, gold, quinine, quinidine, sulfonamides, GP IIb/IIIa Inhibitors
  1. DECREASE
    = thrombocytopenia
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4
Q

What is the main mechanism of Heparin induced thrombocytopenia?

A
  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)
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5
Q

What is ITP?

What is TTP?

A

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..
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6
Q

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
A

Glanzmann’s thrombasthenia

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

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7
Q

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
A

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

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8
Q

What is a storage pool disease?

What is polycethemia vera?

A

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

no aggregation

  1. Acquired disorder of platelets
    - cancer of RBCs which hematocrit increases tremendously
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9
Q

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

A

Platelet function and coagulation are normal.

  • Easy bruising, bleeding from mucosa, purpura, vasculitis.
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10
Q

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).
A
  1. CONGENITAL SUBENDOTHELIAL disorder
    = ehler danlos
  2. Acquired SUBENDOTHELIAL disorder
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11
Q

What is the most common congenital endothelial disorder ?

What are examples of acquired endothelial disorders?

A

Hereditary hemorrhagic Telangiectasia (HHT)

Inflammation, vasculitis (drugs, viruses, Rickettsia)

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12
Q

The following are examples of what?

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

What is a nutritional disorder of the vasculature?

A

Mechanical disorder

  1. Scurvy (vit C deficient)
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13
Q

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

What is the function of protein C?

A

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

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14
Q

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

A

tissue Factor Pathway Inhibitor!

  • Intrinsic pathway: PTT, heparin, hemophilia

Extrinsic: PT, warfarin/coumadin

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15
Q

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

A 
Hemophilia A (Factor VIII)
-8

Hemophilia B (Factor IX) -9

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16
Q

What factors are involved in 12 to 12a conversion?

A

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

17
Q

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

A

EXTRINSIC

18
Q

What stabilizes fibrin and leads to cross-linking?

A

Factor 13 a transamidase

19
Q

What are the vitamin K dependent proteins?

A

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
20
Q

What substances are measured by PT?

APTT?

A

2.5.7.10 and fibrinogen

8,9,10,12

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

21
Q

State the following for Hemophilia A & B:

  1. Transmission
  2. APTT
  3. Platelet count
A
  1. sex linked recessive
  2. APTT IS ELEVATED!
  3. No effect on platelet number
22
Q

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

Describe vwf disease.

A

1 & 3 = decrease in circulating level of factor

2 = QUALITATIVE defect in the protein

vWF
= 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

23
Q

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

  1. APTT
  2. Platelet
  3. Bleeding time
A 
Hemophilias:
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!!!.
24
Q

TPP is due to a defect in what enzyme?

A

ADAMS13

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

25
Q

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

A

BLEEDING

  • Excessive activation of the fibrinolytic system can cause bleeding.
26
Q

How is primary fibrinolysis different from secondary?

What causes each?

A

Primary:

  • 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

27
Q

What is the hallmark of DIC?

A

D- dimer formation

28
Q

Deficiency of a2-antiplasmin results in what?

A

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

29
Q

How does heparin induced thrombocytopenia occur?

How can drug induced bleeding by heparin be controlled?

A
  1. PF-4 forms a complex with heparin, antibodies attack the complex and degrade it
    - thrombocytopenia
  2. Heparin Protamine Sulfate!
30
Q

How are bleeding disorders diagnosed?

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

31
Q

How are the following Thrombophilias diagnosed?

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

32
Q

______ can be increased in diabetes, cancer, inflammation

What is the normal fibrinogen level?

What is the D-dimer test used to diagnose?

A
  1. Plasminogen activator inhibitor (PAI)

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

  1. Fibrinogen normally 400ml/dl

DIC= 200 or 100 ml/dl

  1. D - dimer used to diagnose DIC
33
Q

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
A

APTT
- 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

34
Q

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

DIC
 Hemophilia
Hypercoaguable state
APC Resistance
Von Willebrand disease
A

DIC

35
Q
  1. Splenectomy results in thrombocytopenia or thrombocytosis?
  2. NSAIDS & Aspirin results in quantitative or qualitative changes in platelets?
A

Thrombocytosis

  • platelets are functioning normally and released into circulation
  1. QUALITATIVE changes
    - function is impaired

PHARM/MHD - Exam #4 (20 decks)

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