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• Primary Hemostasis involves vascular and platelet responses to prevent bleeding.

Components of Primary Hemostasis

• Vascular System includes arteries, capillaries, and veins.
• The Vascular System prevents bleeding by diverting blood flow from damaged vessels.
• An additional function of the Vascular System is initiating contact activation of platelets with aggregation.
• Another function of the Vascular System is activating the coagulation system.
• The vascular system contains varying amounts of fibrous tissue made of collagen, elastin, smooth muscle cells, and fibroblasts.
• Thrombopoietin, produced in the liver or kidneys, influences platelet production.
• Platelet maturation from the blast stage typically takes five days.
• Normal bone marrow contains approximately 15 million megakaryocytes.
• This equates to roughly 5 to 10 megakaryocytes per 10x power field when bone marrow smears are microscopically examined.
• Platelets circulate for 8 to 10 days.
• Macrophages remove platelets in the liver and spleen, or by active use in daily coagulation mechanisms.
• Circulating platelets distribute between the spleen (1/3) and blood.
• Patients without a spleen have a higher platelet count, while those with splenomegaly have a lower count.
• The platelet count (or mass) remains constant under normal conditions because of the feedback system that adjusts production to consumption.
• Rebound thrombocytopenia occurs after platelet transfusion.
• Rebound thrombocytosis occurs after platelet depletion.
• Increased megakaryoblast endomitosis from feedback stimulus increases platelet volume and number.
• The feedback stimulus also affects committed unipotential stem cells, which results in more megakaryoblasts.

Events in Primary Hemostasis

• Vasoconstriction is the first response to an injured vessel.
• Serotonin and thromboxane A2, derived from platelets and endothelial cells, initiate vasoconstriction.
• Primary Hemostatic Plug or Platelet Plug formation is part of hemostasis.
• Platelet adhesion refers to platelet adherence to the exposed subendothelial surface.
• Collagen mediates platelet adhesion in vivo, while glass mediates it in vitro.
• Adhesion occurs within 1 to 2 minutes after a break in the endothelium, in the presence of von Willebrand Factor (vWF).
• Glycoprotein (GP1b) acts as a receptor for vWF.
• Activation involves morphologic and functional changes in platelets.
• Agonists that lead to platelet activation include nucleotide (ADP), lipids (TxA2, platelet-activating factor), a structural protein (collagen), and a proteolytic enzyme (thrombin).
• Arachidonic acid is a substrate converted to TxA2 by cyclooxygenase.
• TxA2 is a vasoconstrictor and stimulates platelet secretion.
• Secretion releases platelet granules.
• Alpha granules contain platelet factor, platelet-derived GF, platelet fibrinogen, factor V, vWF, β-thromboglobulin, thrombospondin, fibronectin, and platelet albumin.
• Dense granules include Ca, which is involved in all steps of coagulation, except the contact factor of the intrinsic pathway of secondary hemostasis.
• ADP stimulates platelet aggregation.
• Serotonin acts as a vasoconstrictor.
• Aggregation involves platelet attachment to each other, requiring fibrinogen and Ca.
• The receptor for fibrinogen is Gpllb-Illa.
• End result of these processes is the formation of a primary hemostatic plug or platelet plug.
• Events in primary hemostasis include vasoconstriction, platelet adhesion, platelet activation, platelet secretion, platelet aggregation, and primary hemostatic plug or platelet plug formation.

Platelet Receptor Functions

• Gplb functions as a receptor for vWF.
• Gpllb-Illa functions as a receptor for fibrinogen.
• GpVa functions as a receptor for thrombin.

Disorders of Primary Hemostasis

• Disorders can be a defect in the vascular components or platelet quantitative/qualitative.

Hereditary Connective Tissue Defects

• Ehlers-Danlos Syndrome features increased vascular fragility due to lack of peptidase.
• This peptidase is needed to convert procollagen to collagen.
• Pseudoxanthoma Elasticum involves elastic fibers in small arteries being calcified and structurally abnormal.

Acquired Connective Tissue Defects

• Scurvy is a defect in collagen synthesis due to a deficiency of Vitamin C or ascorbic acid.
• Senile Purpura involves the degradation of collagen and elastin.

Hereditary Alterations of Vessel Wall Syndrome

• Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease) is the most common inherited vascular disorder.
• The blood vessel walls are thin and lack smooth muscle.
• Congenital Hemangiomata (Kasabach-Merritt Syndrome) involves blood vessel tumors.

Acquired Alterations of Vessel Wall Syndrome

• Diabetes Mellitus can cause large vessels to become atherosclerotic.
• Diabetes can also cause capillary basement membrane thickening, blocking normal blood flow.
• Amyloidosis involves the deposition of fibrillar protein (amyloid), causing vessel obstruction.
• Autoimmune Vascular Purpura and Drug-Induced Purpura is endothelial damage that can be caused by Quinine, procaine, penicillin, aspirin, sulfonamides, sedatives, and coumarins.
• Allergic Henoch-Schönlein Purpura is associated with abdominal pain secondary to GI bleeding.
• Schönlein purpura is associated with joint pain.
• Infectious Purpura is endothelial damage caused by bacteria, viruses, and parasites.

Platelet Disorders

• Thrombocytopenia includes decrease in the number of circulating platelets.

Decrease Production

• Aplastic anemia/Pancytopenia involves a decrease in RBC, WBC & platelets.
• Congenital: Fanconi's anemia.
• Acquired: Exposure to radiation, drugs (Chloramphenicol) and benzene.
• Drug Toxicity – Chlorothiazide selectively suppresses the megakaryocyte.
• Myelophthisic process – space-occupying lesion in the bone marrow such as metastatic tumor, fibrosis, or leukemia.

Increased Loss or Destruction

• Dilutional Loss – extensive blood transfusion is often accompanied by thrombocytopenia.

• The degree is directly proportional to the number of units transfused.

• DIC – mass consumption of platelets.

• ITP – autoantibody directed against platelets.

• Acute ITP is the most common cause of thrombocytopenia in children.

• It is acquired after a viral illness such as measles, chickenpox, rubella, or infectious mononucleosis.

• Chronic ITP occurs in adults.

• Increased Platelet Sequestration by Spleen means that Splenomegaly results in 50 - 90% of platelets may be sequestered

• Thrombocytosis refers to an increase in the number of circulating platelets.

Platelet Disorders (Primary Autonomous)

• Primary (Autonomous) Thrombocytosis involves uncontrolled proliferation of platelets
• Characteristics of myeloproliferative disorders.
• Polycythemia vera (PV)
• Essential Thrombocytopenia(ET)
• Chronic myelogenous Leukemia (CML)
• Myelofibrosis with myeloid metaplasia ( MM )

Platelet Disorders (Secondary Reactive)

• Secondary ( Reactive ) thrombocytosis is usually transient.
• Iron Deficiency involves iron inhibiting thrombopoietin.
• Hemolytic annemia acute blood loss due to rapid blood regeneration .
• splenectomy involves increases of platelet count is not 1 - 10 days after splenectomy and peaks 1 to 3 wks later .

Platelet Disorders

• Platelets are hereditary or qualitative

Hereditary Platelet

Platelets are the Platelet Adhesion Disorders . Bernard - soulier's Diease - lacks GP lb associated w?Giant Plates,

• Von Willebrand Disease - lacks Vwf treated Cryoprecipitate
• The Glazmann's Thrombasthemia lacks GM 110,11 A complex for
• In the the Bernard - soulier VWD normally. ADP collagen & Bipineprhre Ristocein abnormally
• Glanzmann's thromboeuthenia normal Ristorelin Adp, Collagen & Bipinepghrins Abnormal
• Platelet secretions alpha granule deficiency
• Platelet large or great.
• dense cubular systems Ca cyckoooygenase . Herminskey Pudalk tyrosines positive olutaneous albinienum

Qualitative Hereditary Platelet secretion

• Dense Granue Deficienies - Hernansky - Pudlask .
• Tyrosine - positivies oculocutaneus accumulation eriod lilie and bleeding tendencies . _ Chedaiak - Higashi - characterized giant lysomes .all cell membrane . wiskalts small cell membrane
• Acquire Uemia toxic melabolites
• Paraporoteminemias abnormal protein
• Acquired AML

Terminology

• Petechiae - purplish red pinpoint hemorrtragic spots<3mm caused by loss of capilary withstand normal pressure & trauma>
• Proportia Hemmorage Blood 1 cm small.mucous membrane
• Deimosis - Blood Escapes skin Mucous Membranes > not deep tissues .
• Epistaxis - is nose bleed.
• Heaarthrosis - Leakage Blood . Joint cavities.
• Hematemesis Vomiting of blood.
• Hematoma swelling or tumor in the tissues.
• Hematuria - Red Blood cell in urine.
• Melena Stool with dark Red or Black Blood.
• Menorrhaiga - Excessive Mensesal bleeding.

LAB

Platelet tests can conduct hemostasis Normal value is 150 - 450 x1099

• Mannual & Automated
• • Sig bleedings occur after the count hits under - 60 9/L
• 20 - 60 minor bruising/Post Operatrwe
• 20 x Skin Mucous most serious bleed - CNS

Bleeding time

• In vivo measure of primary hemostasis NV normal Values 219 " Duke Method - Finger tip or earlobe
• Ivy Method - Pressure - Cuff at 40 mm H11
• platelete function is normal not inreased 100 × 109

platelet Adhesiveness

• Glass bead retention test.

Agreggation

_ In Vitro test to determine the ability of determine platelets to aggregate with cenfuigatinos, ADP collision ritoe

Platelet count

• Tube Use 75 Plastic tubae O D monotored prp at 200

Clot Retraction Time

_ 1 hr and 37 C degrees Retract tube depends

• clof Retract depends an normal numbers of contractile platelets Normal
• • CA normal concentration fibogen
• CASTOR bil Hirsch boccks Formation * diminqlic - Droplat like serum on Blood brod .
• Normal Value is 15 to 45 Minuter

METH

.Uses 3 to 5 mL bliod@C retraction w/ in 24 hrs Normal

• 44 to 67 degrees

Test Test

• • Plateletas increases
• ** 108 mmHG
• grade test
• 1 + Few pelachial on the anieriorface
• • The Moderale test *
• many pelochiae test and hands confluent petechia