Bleeding diathesis dr . Thamir alotaify

1. Bleeding Diathesis Thamir .D Alotaify 1100020

2. Bleeding disorders Def / a group of hematological diseases interfer with normal hemostasis Types : Hypocoagulability - hypercoagulability ( bleeding tendency) ( thrombosis tendency )

3. Normal hemostasis In case of hemorrhage , there will be normal responce to stop the bleeding 1- vasocostriction : Due to : A- direct myogenic spasm B- platelet ( throboxane A2) C- neuronal

4. 2- platelet pulg Mechanism : When there is an endothelial injury Platelet aggregation will takes place When the platelets attatched to each other they will be activated and platelet pulg will occures

5. 3- coagulation cascade 1- coagulation factors 2- prothrombin 3- Ca+

6. 1-Vasopathies I. Congenital • Telangiectasiae (Rendu-Osler-Weber disease) • Aneurysm of fine vessels  • Ehlers-Danlos syndrome, Marfan’s syndrome, retinocerebral angiomatosis (von Hippel-Lindau syndrome), encephalotrigeminal angiomatosis (Sturge-Kalisher-Weber syndrome) II. Acquired • Hemorrhagic vasculitis – Henoch-Schönlein purpura • Immune vasculitis • Systemic vasculitis • Avitaminosis of vitamin C

7. 2- platelet abnormalities : Hypocoagulability : 2- platelet abnormalities : Decrease platelet count → increases bleeding time Viral infections b) Bone marrow failure c) ITP d)TTP e ) Drugs f) Antiphospholipid syndrome

8. 3- Coagulation factors abnormalities 1- anticoagulant drugs 2- decrease production ( hepatic failure ) 3- nephrotic syndrome 4- sepsis 5- vitK defeciency 6- genetic ( hemophilia )

9. I. Congenital • Deficiency of coagulation factor VIII ( hemophilia A) • Deficiency of coagulation factor IX ( hemophilia B) • Deficiency of coagulation factor XI ( hemophilia C) • Deficiency of other coagulation factors (I, II, V, VII, IX, X and XIII)  • Deficiency of XII factor , prekallikrein or kininogen , protein C and S ( without excessive bleeding ) • von Willebrand’s disease ( angiohemophilia )

10. CLINICAL FEATURES OF BLEEDING DISORDERS BY DR.ABDULRAZAQ HUDHAIRI AL-HAZEEMI CONSULTANT NEUROSURGEON GERMAN BOARD SOON ID:1100022

11. Purpura is the appearance of red or purple discolorations on the skin that do not blanch on applying pressure (3–10 mm). A petechia is a small (1 - 2 mm) red or purple spot on the body. An ecchymosis is subcutaneous purpura larger than 1 centimeter . Hemarthrosis is a bleeding into joint spaces. A hematoma is a localized collection of blood outside the blood vessels. Terminology

12. Clinical Features of Bleeding Disorders Platelet Coagulation disorders factor disorders Site of bleeding tissues Skin Deep in soft Mucous membranes (joints, muscles) ( epistaxis , gum, vaginal, GI tract) Petechiae Yes No Ecchymoses (“bruises”) Small, superficial Large, deep Hemarthrosis / muscle bleeding Extremely rare Common Bleeding after cuts & scratches Yes No Bleeding after surgery or trauma Immediate, Delayed ( 1-2 days), usually mild often severe

13. Platelet Coagulation Petechiae , Purpura Hematoma, Joint bl.

14. Petechiae (typical of platelet disorders)

15. Hemarthrosis

16. Hematoma

17. Petechiae

18. Purpura

19. Ecchymosis

20. Senile Purpura Solar purpura or Senile purpura is a skin condition characterized by large, sharply outlined, 1- to 5-cm, dark purplish-red ecchymoses appearing on the dorsa of the forearms and less often the hands.The condition is most common in elderly white persons. It is caused by sun-induced damage to the connective tissue of the skin.

21. Petechiae in patient with Rocky Mountain Spotted Fever Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by the organism Rickettsia rickettsii .

22. Henoch-Schonlein purpura Henoch-Schoenlein purpura is an acute immunoglobulin A ( IgA )–mediated leukocytoclastic vasculitis that primarily affects children.

23. Ecchymoses (typical of coagulation factor disorders)

24. Coagulation profile Amir Mohammed

25. Coagulation Profile OVERVIEW Prothrombin Time Activated Partial Thromboplastin Time Thrombin Time Fibrinogen Fibrin Degradation Products (FDP’s) APTT 50% NP Retiplase Time Euglobin Lysis Time Urea solubility Test

26. PROTHROMBIN TIME This measures the clotting time of plasma after the addition of brain extract containing tissue thromboplastin . This will test the extrinsic clotting pathway involving factors V, VII, X and Fibrinogen . The reference range for prothrombin time depends on the analytical method used, but is usually around 12-13 seconds Prolongation of the Prothrombin Time is seen in, Liver cell dysfunction Vitamin K deficiency Warfarin therapy Disseminated Intravascular Coagulation (DIC)

27. ACTIVATED PARTIAL THROMBOPLASTIN TIME This will test for defects in the extrinsic pathway. The clotting factors are Factors, XII, XI, IX, VIII, X, V, II and I The typical reference range is between 30 seconds and 50 s Prolongation of APTT is seen in, Haemophilia A and B (Factors VIII and IX) Von Willebrandt's Disease (stabilizing factor for factor VII  ed ) Other factor deficiencies (XII, XI) Liver failure Disseminated Intravscular Coagulation.

28. THROMBIN TIME thrombin added to undiluted plasma tests the conversion of fibrinogen -> fibrin The reference ranges of the Thrombin Clotting time is generally <22 seconds, prolonged in: -> heparin -> DIC -> hypofibrinogenaemia -> fibrin degradation products

29. FIBRINOGEN normal: 1.5-4.0 high in: acute phase response low in: -> sepsis -> DIC FIBRIN DEGRADATION PRODUCTS (FDPs) marker of fibrin and fibrinogen breakdown The reference range of FDP levels is less than 10 mcg/ mL (conventional units) or less than 10 mg/L (SI units).

30. APTT 50% NP mixing of patients sample with pooled normal plasma – 50:50 mix failure to correct after mixing: -> lupus anticoagulant ECHIS TIME snake venom from Echis multisquamatus added to sample differentiates liver dysfunction from vitamin deficiency this activates prothrombin without requiring vitamin K is normal in vitamin K deficiency or warfarin use The reference ranges is 10.5 - 15 sec if prolonged: -> factor deficiency (liver disease)

31. RETIPLASE TIME used to detect deficiency or abnormalities in fibrinogen snake venom that has similar action to thrombin but is resistant to inhibition by antithrombin III interpret with TCT if retiplase time normal and TCT prolonged: -> heparin -> hirudin -> direct thrombin inhibitors

32. EUGLOBIN LYSIS TIME shortened time: -> presence of systemic fibrinolytic pathway activators UREA SOLUBILITY TEST factor 13 stabilises fibrin if deficient 5M urea will dissolve it

33. Treatment By:fahad saad alenzi 1100026

34. Children: Children do not usually require treatment, Where this is necessary on clinical grounds . high-dose prednisolone is effective, given for a very short course . Intravenous immunoglobulin ( i.v . IgG ) should be reserved for very serious bleeding or urgent surgery . Chronic ITP is rare and requires specialist management .

35. Adults: Patients with platelet counts greater than 30 × 10^9/L require no urgent treatment unless they are about to undergo a surgical procedure.

36. First-line therapy : consists of oral corticosteroids 1 mg/kg body weight . Approximately 66% will respond to prednisolone but relapse is common when the dose is reduced. Only 33 % of patients can expect a long-term response and long term remission is seen in only 10–20% of patients following stopping prednisolone . Patients who fail to respond to corticosteroids or require high doses to maintain a safe platelet count should be considered for splenectomy .

37. Intravenous immunoglobulin ( i.v. IgG ) is effective, It raises platelet count in 75% and in 50% the platelet count will normalize , Responses are only transient (3–4 weeks) with little evidence of any lasting effect . However, it is very useful where a rapid rise in platelet count is desired, especially before surgery . There are also advocates for high dose corticosteroids for additional therapy.

38. Second-line therapy: involves splenectomy , to which the majority of patients respond – two-thirds will achieve a normal platelet count . Patients who do not have a complete response can still expect some improvement.

39. Third-line therapy; For those that fail splenectomy , a wide range of other therapies are available, These include; highdose corticosteroids , intravenous immunoglobulin, vinca alkaloids, danazol , Immunosuppressive agents such as ciclosporin and dapsone . combination chemotherapy, mycophenolate mofetil .

40. Major difficulties with many third-line therapies are modest response rates and slow onset of action , Consequently ,there is also interest in the use of specific monoclonal antibodies such as rituximab, as well as recombinant thrombopoietin .

41. However, clinical trials of thrombopoietin were stopped because of thrombocytopenia but eltrombopag a thrombopoietin receptor agonist (which binds to another point of the thrombopoietin receptor), has been shown to increase platelets in ITP.

42. Romiplostim ; a novel thrombopoiesis protein given weekly subcutaneously, has also been shown to significantly increase platelet count in ITP on a long-term basis, there were no major adverse effects in this trial. Platelet transfusions are reserved for intracranial or other extreme haemorrhage , where emergency splenectomy may be justified.