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56 Cards in this Set

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Process that:


1. Retains the blood w/in the vascular system during periods of injury


2. Localizes the reactions involved to the site of injury


3. Repairs and re-establishes blood flow thru the injured vessel

Hemostasis

Steps in Hemostatic Response:

1. Injury to Endothelium (vessel)


2. Primary Hemostasis


3. Secondary Hemostasis


4. Fibrinolysia

2. Formation of primary hemostatic plug (plts have main role)


3. Formation of fibrin clot (coag proteins, major contributor


4. Removal of Clot

Primary Hemostasis

1. Vasoconstriction


2. Platelet Adhesion


3. Platelet Aggregation (primary hemostatic plug at site lf injury)

Blood Vessels & Plts


are involved

Interaction of coagulation factors to produce fibrin (secondary hemostatic plug)


Fibrin Stabilization by Factor XIII

Secondary Hemostasis

End Product: Fibrin Clot

Fibrinolysis:

1. Release of Tissue Plasminogen Activator


2. Converaion Plasminogen to Plasmin


3. Conversion of Fibrin to Fibrin Degradation products

Vascular System

1. Arteries


2. Veins


3. Capillaries

Platelets: Formation of Primary Hemostatic Plug

When vascular injury occurs, platelets come in contact w/ subendothelium (collagen, fibronectin) and adhere to portion of it

Platelet Adhesion

Occurs in the presence of vWF (von Willebrand Factor)

Morphologic and functional change in platelets

Platelet Activation

Cyclooxygenase (frm plt) metabolize arachidonic acid to form prostaglandin endoperoxides converted to TXA2

Inactivates enzyme cyclooxygenase

Aspirin

A potent vasoconstrictor and a platelet stimulator, causing platelet secretion and aggregation

Thromboxane A2 (TXA2)

Platelet granules move to the center of the plts and fuse with open canalicular system connected to the outside of the platelet; in this way the content of granules are extruded outside

Platelet Secretion

Following activation the platelet undergoes a shape change caused by contraction of

Microtubules

Change from Disk to Spherical Shape w/ extrusion of numerous pseudopods

Alpha Granules:

1. Platelet Factor 4


2. B-thromboglobulin


3. Platelet Derived Growth Factor (PDGF)


4. Thrombospondin


5. vWD


6. Fibrinogen


7. Fibronectin


8. Factor V

Dense Granules:

1. ADP


2. ATP


3. Serotonin (5-HIAA)


4. Pyrophosphate


5. Magnesium


6. Iron

Substances that promote Coagulation:

1. HMWK


2. Fibrinogen


3. Factor V


4. Factor VIII:vWF

All are found in


Alpha Granules



Factor V - Cofactor in Fibrin clot formation


Fibrinogen - Converted to FIBRIN for clot formation

Contact activation of intrinsic coagulation pathway

HMWK

Assists platelet adhesion to subendothelium to provide coagulation surface

Factor VIII:vWF

Promotes Aggregation:

1. ADP


2. Calcium


3. PF4


4. Thrombospondin

Promotes Vasoconstriction:

1. Serotonin


2. TXA2

Promotes Vascular Repair:

1. PDGF


2. B-thromboglobulin

PDGF - promotes smooth muscle growth for vessel repair


B-thromboglobulin - Chemotactic for fibroblasts to help in vessel repair

Precursor to plasmin, which induces clot lysis

Plasminogen

Plasmin Inhibitor, inhibits clot lysis

A2-Antiplasmin

Complement System Inhibitor

C1 Esterase Inhibitor

Platelet Stimulating Agents

1. Epinephrine


2. Collagen


3. Thrombin


4. ADP

Platelets adhernce to one another caused by platelet stimulating agents

Platelet Aggregation

Fibrinogen - necessary as cofactor for platelet aggregation

Most common inherited vascular disorder


Localized dilation of the walls of the small blood vessels (thin & lack smooth muscles) of the skin and mucous membranes

Hereditary Hemorrhagic Telangiectasia/ Osler-Weber-Rendu Syndrome

Disorder Associated w/ tumors composed of blood vessels that commonly swell and bleed at the surface

Congenital Hemangiomata/Kasabach-Merritt Syndrome

Ehlers-Danlos Syndrome

1

Marfan's Syndrome

1

Connective tissue elastic fibers in small arteries are calcified and structurally abnormal

Pseudoxanthoma Elasticum

Loss of elsticity of the skin


Bruised areas commonly found on the forearms of elderly persons

Senile Purpura

Dec Collagen, Elastin

Acquired defect in synthesis of collagen & hyaluronic acid


Ascorbic Acid Deficiency

Scurvy

Immunologic damage to endothelial cells


Gastrointestinal hemorrhage and joint swelling occur w/ purpuric rash

Henoch-Schonlein Purpura

Most common in children


Often follows Respiratory Infection

Quantitative Platelet Disorders

1. Thrombocytopenia - Dec


2. Thrombocytosis - Inc

Causes of Thrombocytopenia:

1. Dec Plt Pxn


2. Dec Survival Time


3. Inc Plt Sequestration by Spleen (Splenomegally)


4. Dilution of Plt count


(Massive Transfusion)

Degree of thrombocytopenia is directly proportional to the number of unita mms transfused

Dec Plt Pxn seen in:

1. Aplastic Anemia


2. Congenital: Fanconi's Anemia


3. Acquired: Radiation, Chemical, Drugs, Benzene

Chloramphenicol


- Antibiotic of last resort


- Causes Aplastic Anemia



Aplastic Anemia


-Pancytopenia, Dec RBC, WBC, PLTS

Dec Survival time due to Inc Destruction

1. DIC


2. ITP

DIC


- Mass consumption


ITP


- D/t auto-antibodies to plts

Moderate Inc in Plts, Asymptomatic


Seen After: Hemorrhage, Splenectomy, Blood Loss

Reactive


Thrombocytosis

Inc RBC Inclusion

Marked Inc in Plts


Assoc w/ Thrombotic/Hemorrhagic Complications

Autonomous Thrombocytosis

Plt Count of >1000 x 10^9/L


Plt Function is Abnormal

Essential Thromobocythemia

Autosomal Recessive Trait


Platelets Lack GpIb


Giant Platelets, upto 20 um in diameter

Bernard-Soulier Syndrome

Normal Aggregation w/: Epinephrine, ADP, Collagen


Dec Aggregation w/: Ristocetin

Autosomal Recessive Trait


Dec or Absence of GPIIB-IIIa complex

Glanzmann's Thrombasthenia

Normal Response w/: Ristocetin


Defective Primary response in presence of: ADP, Collagen, & Epinephrine

Von Willebrand's Disease

Normal w/: Epinephrine, Collagen, & ADP


Dec aggregation w/: Ristocetin

Qualitative Plt Disorders:

1. Platelet Adhesion


-vWD


-Bernard-Soulier Syndrome


2. Platelet Aggregation


-Glanzmann's Thrombasthenia


3. Platelet Secretion


Release Disorders (Storage Pool Defects)


Alpha Granule Def: Gray Plt Syndrome, Quebec


Dense Granule Def: Hermansky-Pudlak, Chediak Higashi, WAS

Alpha Granule deficiency which there is deficiency of Factor V Binding Protein or

Quebec Dse

Acquired Plt Disorders:

1. Uremia


2. Paraproteinemia


3. Acute Myeloblastic Leukemia


4. Myeloproliferative Disorders


5. Drugs

Acute Myeloblastic Leukemia


- Megakaryocytes in the BM may be small & abnormal

Metabolites that are toxic to the platelets accumulate in Plasma

Uremia

Coating of platelet membrane w/ abnormal proteins

Paraproteinemia

1. MM


2. Waldenstrom's Macroglobulinemia

Primary Assay to Determine alterations in Plt Function


In vitro test to determine ability of plts to aggregate w/ certain aggonists

Platelet Aggregation

Platelet Aggregometer



PRP = Centri= 50g for 30 Mins


Platelet Agonists:


1. Epinephrine


2. Collagen


3. ADP


4. Ristocetin



PRP + Agonist = O.D. Monitored

Measure ability of platelets to adhere in glass surfaces

Platelet Adhesiveness (Salzmann)

Requires normal number of functioning platelets, calcium, ATP, & Normal Fibrinogen Level


Test for Function of Plts

Clot Retraction Time

Methods:


1. Castor Oil/Hirschboeck


2. Stefanini


3. MacFarlane

Clot Retraction Time method observed for the formation of dimpling/droplet like serum on the surface of blood drop

Castor Oil/Hirschboeck Method

Initial Work up for vWD

1. CBC


2. PT


3. PTT

Blood Film taken from Capillary Puncture

Poor Man's Aggregation Test

Primary Hemostasis screening test


for platelet & vascular function


Original Test of Platelet Function

Bleeding Time

*Maybe prolonged in severe fibrinogen def/afibrinogenemia



Methods:


1. Duke


2. Ivy

Bleeding Time Method in which a


1. Blood pressure cuff is inflated to 40 mmHg


2. Calibrated spring-loaded lancet was triggered on the volar surface of forearm a few inches distal to the antecubital crease


2. Resulting wound was blotted every 30 Secs w/ filter paper until bleeding stops

Ivy Method