Pathophysiology of Hemostasis Case 1 A 11 year old patient complains of pain in the knee joint after a bruise,general weakness, quick

fatigue. From his medical history it is known that the child often has profuse nose bleeding. On examination an extensive underskin hematoma in the left knee joint and on the front surface of the cnemis was found. The left joint is enlarged, its movements are painful. Laboratory findings: Hb 50 g/L, erythtrocytes 3.5 x 10 /l, leucocytes 9.0 x 10 /l, platelets 250 x 10 /l: bleeding time(Duka assay) 3 min: aggregation of platelets is not disturbed: test for blood resistance is negative: time retraction of blood cot is within the norm: blood clotting time 20 min: prothrombin time and content of fibrinogen are within the norm: factor V111 content in plasma is sharply decreased. Questions: 1.What pathogenesis of hemorrhagic syndrome development does the child have? - Hemophilia A (x-linked disorder male disorder) -disturbance of secondary hemostatic mechanism at 1st step (synthesis of prothrombinase) -in result increase blood clotting time(20 min) -bleeding time in primary hemostasis is normal(3 min) -anemia disease(decrease Hb 50 g/l) -hematoma type develop after 2 or 6 hrs bcoz mechanism of primary hemostasis is to stop bleeding,secondary occur after that develop f(x). ~knee joint (hemarthrosis) ~underskin ~other cavities maybe severe bleeding 2.What is the treatment of this syndrome? - purification of XII 3.Indicate the basic factors causing the development of hemorrhagic syndromes. -massive hemorrhage after trauma -hereditary (carrier:mother) Case 2 20 yr old, girl c/o: -profuse bleeding from wound at the place of tooth extraction made 5 hours before. -medical history : frequent nose bleeding, longstanding, non-stopping bleeding on superficial damage of the skin, profuse bleeding during menses were registered. findings on examination: - heart rate 120b/m - BP 100/60mmHg - liver and spleen not enlarged lab findings: - Hb: 80g/L - RBC: 3.6x1012/l - Color index: 0.62 - platelets: 40x109/l -many platelets have atypical form, life span decrease to few hours. Blood clotting time (Duke assay) is 15 minutes -test of blood vessels resistance is positive -retraction of blood slowed down. -quantity of IgG3 increased. -diagnosis based on examination : autoimmune thrombocytopenia (diease of Verlholf). Prescription: corticosteroids (led to decrease of severity of hemorrhagic syndrome and increase platelet quantity)

1.Explain the mechanism of hemorrhagic syndrome development. Identify type of bleeding. Type of bleeding : spontaneous. Mechanism: Decrease antiplatelets

 Activation of autoimmune (antigen dependent cytotoxic HS type 2) Decrease in resistance of vessels walls Platelet decrease hence less supplying the EC EC deficiency Can see echymose on skin when using tourniquet (due to decrease resistance of vessels)

2. How will the production of thrombocytopoetins change? By increasing stimulation of production of thrombocyte in bone marrow. 3. Explain the positive dynamics of this disease after prescription of cortisteroids. Corticosteroids acts as anti-inflammatory drug.

Case 3 A 60-year-old patient was admitted to hospital after a hypertonic crisis with complaints of severe headache, feeling of heaviness in the occiput, memory weakening, vision deterioration. Laboratory findings : increase of antihemophilic globulins level ( factor VIII etc.); increase of the content of fibrinogen, cholesterol and b-lipoproteids; decrease of protein C activity as well as prostacycline (PGIz) and tissue plasminogen activator (t-PA) synthesis. A day later the state of the patient worsened, he lost consciousness; left-side hemiparesis developed. The diagnosis : cerebral atherosclerosis complicated by thrombosis of the right middle brain artery. Questions: 1. Indicate the factors promoting thrombus formation. 1.Injury of endothelial cell 2,.increase pressure 3.damage endothelial cell 4.decrease prostacycline (Pgi2) 5.blood clotting

2. How are rheological features of the patient's blood altered and why? -additional substance in blood(cholesterol,b-lipoproteids) 3. Enumerate the principles of pathogenetic therapy of thrombosis. -1.anticoagulant protein c 2.antiaggregantsthrombomodulin 3fibrinolytic preparation-.streptokinase 4.vasodilators Case 4 20 yr old woman admitted to gynecology clinic - uterine bleeding, developed after a criminal abortion Lab findings: -erythrocytes 3.6 x 1012/L -platelets 40x109/L -prothrombin index 80% -blood clotting time 20min -activated forms of platelets and their aggregates in peripheral blood found -content of fibrin split products in blood was increased Finding examination: -BP80/60 mmHG -Heart rate120 b/m In Blood: Increase content of residual nitrogen as a result of acute renal failure dev, metabolic hyperacidity. 1. Enumerate the important causes of DIC (disseminated intravascular coagulation)

In result of septic shock[criminal arbotion] Endotoxin Large injury in endothelial cell[Factor IIIactivate clotting] Disseminate small clotting Block microcirculating thrombus Disturbance in microcirculatory especially in organ (Kidney, Brain, Lung) 2. Sequence of events in DIC development after massive tissue destruction 1st stage Hypercoagulation (primary and secondary) Disseminated of coagulation clot 2nd stage Increase consumption of platelet Cause hemorrhage 3rd stage Level of platelet decrease (thrombocytopenia) Hypocoagulate with active fibrinolytic system Complication:-severe bleeding -decrease platelet -activation protease systemfibrinolysisdestruction procoagulant protein

endothelial injuryactivation of coagulation sequencesformation of thrombi in microcirculationconsumption of platelets and coagulation factors plasma clotting factor level activation of fibrinolysis Obstetric complications (most common cause), with chemicals from the uterus being released into the blood, or from amniotic fluid embolisms, and eclampsia can be causes. Another obstetric condition which can cause DIC is abruptio placentae. Sepsis, particularly with gram-negative bacteria. Tissue trauma (massive tissue destruction) such as burns, accidents, surgery or shock. Malignant cancers, or widespread tissue damage (e.g. burns), or hypersensitivity reactions all can produce the chemicals leading to a DIC. Liver disease Incompatible blood transfusion reactions Envenomation by some venomous snakes such as the Stephens Banded Snake, Hoplocephalus stephensi (from the family of Elapidae).

3.Explain mech of bleeding syndrome development activate primary & secondary hemostasis (hypercoagulative) disiminated of coagulation clot consumption of platelet platelet count (thrombocytopenia) procoagulant (prpthombin) consumption coagulopathy (may dev hemorrhage) hypercoagulate

Case 5 A 7 y/o child was admitted to hospital with complaints of skin eruption, his urine had red color. He had undergone treatment for flu at home: for 10 days he had taken aspirin three times a day to decrease temp. Findings on d front surface of both examination: multiple symmetrical popular-hemorrhagic eruption on d front surface of cnemis, around d knees and ankle joints, macrochematuria. Lab finding: circulating immune complexes in blood, d quality of platelets, bleeding (Duke assay), blood clotting time within d norm; retraction of blood clot & stimulated aggregation of platelets undisturbed. The test for blood vessels resistance was +ve. The diagnosis: hemorrhagic vasculitis.

Question: 1.Explaint d mech of hemorrhagic syndrome developement - hemorrhagic vasculitis immuno-complex mediated hypersensitivity (type 3) - mech: antigen: exogenous foreign protein of virus, drugs re-exposure of antigen immuno-complex formation (complexes are small, formed in slight antigen excess, which find less avidly to phagocytic cell & therefore circulate longer) accumulation & deposition(precipitation) into vessels [vasculitis] result of disturbance of m/circulatory in various tissue (renal glomeruli, joint, skin, heart, serosal surface, small BV)

2. How does thromboresistance of BV change after their damage? Why?

3.Name d principle of pathogenetic therapy of this hemorrhagic syndrome - Heparin therapy was instituted as subcutaneous injections 4 times daily