REVIEW- CLASSIC VS MODERN

Transcription

1 HEMOSTASIS 2

2 REVIEW- CLASSIC VS MODERN

3 ANTICOAGULANT THERAPY Injectable- heparin and heparin derivatives Unfractioned heparin Low molecular weight heparins Oral- antivitamin K inhibitors Coumadins- most used= WARFARIN

4 HEPARIN AND HEPARAN SULFATE Heparan sulfate- is a GAG Similar structure to heparin Endogenous heparin- secretory granules of mast cells (probably being negatively chargedretains histamine inside) Function of heparan sulfate in coagulationanticoagulant- receptor for ATIII activation thrombin inhibition

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6 TYPES OF HEPARIN Unfractioned- high molecular weight; injectable iv, hospitalised patient usually, APTT monitoring needed (administred using a heparin pump) Low molecular weight heparin- subcutaneously, home therapy, no APTT monitoring, less bleeding as side effect

7 UNFRACTIONED HEPARIN AS A DRUG Needs ATIII as a cofactor Inhibits Xa and thrombin Clinical uses Venous thrombosis disorders Pulmonary embolism Prophylaxis and treatment- thrombosis in major surgeries Extracorporeal circulation Blood samples drowned for lab purpuses- AC Blood transfusions- in vitro AC

8 LOW MOLECULAR WEIGHT HEPARIN USE No APTT monitoring needed Lower molecular weight May be administrated subcutaneously- may be used for unhospitalized patients (once/twice a day) Less bleeding Tend to replace heparin in venous thrombosis, pulm embolism, acute coronary syndomes

9 ORAL ANTICOAGULANT THERAPY Vitamin K competitors- coumadin (Warfarin) Warfarin inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S.

10 VITAMIN K DEPENDENT FACTORS

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12 In the liver- vitamin K helps the carboxylation of glutamic acid residues on immature coag factors; in this process it gets oxidized Antivitamin K drugs inhibit reductase by inhibition, vitamin K stays in an inactive form

13 ANTI VITAMIN K Anticoagulant effect starts in h from initiation stops in h after it is stopped Oral treatment At first- injectable treatment overlaps the oral one

14 ANTIVITAMIN K CLINICAL USES Venous thrombosis Stroke Thrombembolism Cardiac valve replacement Post myocardial infarction

15 MONITORING HEMOSTASIS Primary Bleeding time Rumpel Leede PLT count Secondary Clotting time Howell Gram time APTT PT (Quick time)

16 HOWELL GRAM INTRINSIC AND COMMON test explores the intrinsic and common pathways; for this we add CaCl2 to citrate plasma and start monitoring the time needed to clot. Normal values= s High: TR disfunction / thrombocytopenia intrinsic pathway factor deficit (XII,XI,IX,VIII- hemophilia) common pathway deficit- X, V, II, I (hypofibrinogenemia/ afibrinogenemia) -anti- clotting therapy- heparin

17 APTT ACTIVATED PARTIAL THROMBOPLASTIN TIME INTRINSIC AND COMMON PATHWAYS To citrate plasma (with low amount of plateletscentrifuge for 15 min rpm) we add Ca Cl2, kaolin, cephalin and start monitoring the time needed to clot. Cephalin is a partial tromboplastin (only phospholipid) Kaolin or silica is a negatively charged molecule activates factor XII Normal values = s Causes of abnormal high values- the same as Howellexcept for the platelet- derived causes It is affected by unfractioned heparin- used to monitor therapy

18 APTT

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20 APTT INTERPRETATION- PROLONGATION Deficiencies of XII,XI,IX,VIII (but in mild def is normal- the def factor needs to be <20-40% for aptt to be low) Antibodies against fviii (aquired hemofilia) or lupus anticoagulant present Liver disease Unfractioned heparin use

21 PROTHROMBIN TIME (QUICK METHOD-PT/QT) EXTRINSIC AND COMMON To citrate plasma (with high amount of platelets) we add Ca Cl2, thromboplastin and start monitoring the time needed to clot. Elevated in Deficit of I, II, V, VII, X factors Liver failure K vitamin deficiency/ anti vit K anticoag therapy Normal values = s

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23 PROTHROMBIN TIME Used to monitor therapy with oral anticoagulant drugs- vitamin K blocking agents- coumarins (warfarin)!!! By INR fraction which should be measured constantly in these patients The therapy is used in patients with high thrombotic risk

24 INR International normalized ratio ISI- depends on the tissue factor, it is established by the manufacturer (usually between 1-2) Normal range for a healthy person= Warfarin therapy monitoring- depends on pathology

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27 FIBRINOLYSIS As the clots forms, it incorporates plasmin molecules. Plasmin is an enzyme formed from plasminogen by tissue plasminogen activator (t-pa) and urokinase type plasminogen activator (u-pa) Plasmin breaks down fibrin polymers into fibrin fragments = fibrinolysis Fibrinolysis helps removing the clot as the repair processes occur.

28 FIBRINOLYSIS Damage to the tissues releases TPA, which together with activated components from the coagulation pathways and protein C, activates plasminogen to plasmin. Plasmin acts on the insoluble fibrin to form a series of soluble products: FDPs. Fibrin that has been stabilized (crosslinked) by factor XIII gives rise to crosslinked FDPs (XDPs), as well as X Y D and E fragments. The XDPs (D-dimer, D-dimer-E fragments), and oligomers of fragments X and Y, can be detected using antibody coated latex beads.

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30 PLASMINOGEN Zymogen plasmin GP Syntesized in liver Lyses fbrin into fibrin degradation products (FDP) and D- dimer

31 PHYSIOLOGICAL ACTIVATORS OF PLASMIN tpa- released from entoth cells responsable for intravascular fibrinolysis- mainly activates plasminogen bound to fibrin upa- high conc in urine responsible for extravascular fibrinolysis

32 PHYSIOLOGICAL INHIBITORS OF PLASMIN PAI-1 is the physiological plasminogen activatior inhibitor 1- (tpa)- from platelets Alpha 2 antitripsin- inhibits plasmin directly

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34 FIBRINOLYTIC THERAPY= THROMBOLYTIC Used to dissolve blood clots- act by plasminogen activation 3 major classes: tpa used in miocardial infarction therapy upa spa (streptokinase activator)

35 CLINICAL CASE 1 23 year old male. Over the past week noted increasing fatigue, sore throat, earaches, headaches, and episodic fever and chills. Unable to run his customary 25 miles per week. Erythematous throat and tonsils. Swollen cervical lymph nodes.

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37 DIAGNOSIS INFECTIOUS MONONUCLEOSIS kissing disease Viral- Ebstein Barr virus 90% asymptomatic Pharyngitis, fatigue, malaise, fever

38 CASE STUDY 2 70 year old female. Symptoms of dyspnea on exertion, easy fatigability for past 2 to 3 months. Physical exam- palor

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40 DIAGNOSIS- IRON DEFICIENCY ANEMIA

41 CASE STUDY 3 25 year old male. Recurrent upper respiratory infections with fever, nausea, and submandibular swelling for several months prior to admission. Noted that cuts on his hands did not heal well. Physical Exam Submandibular adenopathy. No other organomegaly.

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43 DIAGNOSIS ACUTE MYELOBLASTIC LEUKEMIA

44 CASE STUDY 4 40 year old female. Brought to Emergency Room with symptoms of severe frontal headache and associated confusion. Noted to have decreased energy level and a 15 pound weight loss over the previous three months. Physical Exam Pale appearing, but otherwise within normal limits. No organomegaly.

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46 CASE STUDY 5 11 year old male. Presented in emergency room with recent onset of easy bruising, bleeding gums Previously in excellent health. Mother stated he was "never sick before in his entire life." No history of recent viral infection, and no family history of bleeding disorders.

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48 HEMOSTASIS: Bleeding time= 10 min INR 0.91 (RI ) Howel Gram 2 min PTT 24.8 sec (RI 23-34) TT 15.8 sec (RI 13-18)

49 IMMUNE THROMBOCYTOPENIC PURPURA

50 CASE STUDY 6 History 54 year old female. One year history of fatigue, weight loss, and increasingly severe back pain. Physical Exam She appeared pale, but otherwise her physical exam was within normal limits.

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52 PROTEIN ELECTROPHORESIS Total protein 11.0 g/dl (RI ) Serum protein electrophoresis: Albumin 3.2 g/dl (RI ) Globulins: Alpha1 0.4 (RI ) Alpha2 1.0 (RI ) Beta 0.8 (RI ) Gamma 5.6 (RI )

53 Immunoglobulins, quantitative: IgA 9 mg/dl (RI ) IgG 5800 mg/dl (RI ) IgM 25 mg/dl (RI ) Fibrinogen 650 mg/dl ESR 70 mm/h

54 MULTIPLE MYELOMA

55 CASE STUDY 7 History 75 year old male. Symptoms of severe headache and generalized pruritis. Physical Exam Spleen palpable 10 cm. below left costal margin. Liver palpable 3 cm. below right costal margin. The rest of the exam was within normal limits.

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57 PULMONARY FUNCTION: Oxygen saturation: 97% (RI )

58 POLYCYTHEMIA VERA

59 PRACTICE QUESTIONS

60 BLOOD 1. is a type of connective tissue 2. is involved in the process of homeothermy 3. bicarbonate buffer system is the most important extracellular system 4. ADH helps at the reabsorption of Na+ in the distal nephron

61 HEMATOCRIT 1. somatic hematocrit is higher than the venous one 2. represents the % of formed elements in the blood 3. blood viscosity is inversely proportional to the hematocrit value 4. splenic venous blood has the highest value

62 PLASMA PROTEINS 1. albumin is the main contributor to oncotic pressure 2. the normal concentration of albumin is 7 g/dl of blood 3. ceruloplasmin is a copper carring protein 4. albumin is a positive acute phase protein

63 IMMUNOGLOBULINS 1. IgM is released during primary humoral response 2. IgG may cross the placenta 3. IgA is important in local mucosal immunity 4. IgE trigger alergic reactions

64 ESR is directly proportional with blood viscosity low ESR can be encountered in anemia it s measured after centrifuging the blood at 3000 RPM detects non-specific inflammation

65 RED BLOOD CELLS 1. 1 g of Hb can transport 1.34 ml of oxygen 2. MCV =120fL showes that there are macrocytes present in the blood 3. 70% of the iron in the organism is found in hemoglobin 4. when pco2 is low, red blood cells release O2 more easely to the tissues

66 WHICH OF THE FOLLOWING ARE PART OF THE SPECIFIC IMMUNE ANSWERS 1. first line of defense mechanisms 2. second line of defense 3. all three lines of defense 4. third line of defense

67 CHOOSE THE RIGHT MACROPHAGES FUNCTIONS 1. antigen presenting cells 2. initiation of humoral immune answer 3. initiation of celular immune answer 4. they are the first cells to respond to tissue infection

68 ANTIBODIES WORK AS 1. opsonins 2. antitoxins 3. agglutinate bacteria 4. stimulate perforin- pores formation in antigenic cell membrane

69 FORMS OF CO2 TRANSPORT IN THE BLOOD ARE carbaminohb bound to albumin bicarbonates carboxyhb

70 CHOOSE THE RIGHT CONDITIONS WHICH SHIFT THE OXYHB DISSOCIATION CURVE TO THE RIGHT Hb has low affinity for oxigen high 2,3 DPG low ph low temperature

71 WHAT WOULD BE THE ERYTHROCYTE INDICES PROFILE FOR A PERSON WITH NORMOCHROMIC MACROCYTIC ANEMIA 1. MCHC= 28 g/100 ml 2. MCHC= 35 g/100 ml 3. MCV= 80 fl 4. MCV= 120 fl