clinical approach to patients with bleeding tendency

this presentation explains the physiology of hemostasis, in addition to the clinical approach for patients presenting with bleeding tendency.

1. A pproach to patients with bleeding tendency Reem Alyahya 212522156

2. Introduction: hemostasis involve a complex interplay among vascular integrity, platelet number and function, coagulation factors, and fibrinolysis . When the patient present with bleeding that is spontaneous, excessive, or delayed in onset following tissue injury bleeding tendency is suspected and should be investigated.

3. Physiology of hemostasis:

4. Primary hemostasis Primary hemostasis involves interactions between the vessel wall and the blood platelets, terminating in the formation of a primary hemostatic plug

5. Primary hemostasis Defects in primary hemostasis can be due to platelet or vascular disorders . Platelet disorders are quantitative (thrombocytopenia) or qualitative ( thrombopathia ). Vasculopathies can result in excessive fragility, or abnormal interaction with platelets

6. Secondary hemostasis Secondary hemostasis involves the formation of fibrin, in and around the primary hemostatic plug. “ coagulation cascade “

7. Secondary hemostasis Defects of secondary hemostasis may be due to quantitative or qualitative coagulation factor disorders. E.g. liver disease , Vitamin K deficiency

8. Fibrinolysis The fibrinolytic system consists of plasminogen and all activators that convert it to its active form, plasmin. Plasmin is responsible for dissolution of the fibrin clot

9. Diagnostic approach to patients with bleeding tendency

10. Diagnostic approach Once the patient has been stabilized, every effort should be directed toward the rapid establishment of a diagnosis. The clinician must answer 3 initial questions: Is the bleeding due to local factors, or a generalized bleeding disorder ? Is the defect congenital or acquired? If a systemic disorder does exist, what is the nature of the hemostatic defect ? “ Vascular/platelet defect (primary hemostasis) or coagulation defect ( s econdary hemostasis) “

11. History I   Is there a generalized hemostatic defect ?

12. History II Is the defect congenital or acquired ? A family history of a bleeding disorder should be sought. Severe inherited defects usually become apparent in infancy. while mild inherited defects may only come to attention later in life, for example with excessive bleeding after surgery, childbirth, dental extractions or trauma . Some defects are revealed by routine coagulation screens which are performed before surgical procedures.

13. History III   Is the bleeding suggestive of a vascular/platelet defect or a coagulation defect? Vascular/platelet bleeding Coagulation disorders easy bruising bleeding after injury or surgery spontaneous bleeding from small vessels haemarthroses and muscle haematomas bleeding into the skin “ petechiae and ecchymosis “ Bleeding from mucous membranes e.g. the nose and mouth.

14. History VI Medication history: including prescribed medications, over-the-counter medications, and herbal products. Drug ingestion may be associated with a bleeding diathesis via a variety of mechanisms, such as the induction of thrombocytopenia or platelet dysfunction, aplastic anemia, or vascular purpura . In addition, some drugs can induce or exacerbate a coagulation disorder. Examples include platelet dysfunction induced by aspirin. beta-lactam antibiotics , clopidogrel .   the co-ingestion of drugs that may potentiate the anticoagulant effects of warfarin.

15. Physical examination: The distribution, extent and nature of current hemorrhage should be noted in an attempt to determine if the bleeding is due to local causes or a systemic bleeding disorder. The presence of hemorrhage in more than one site is suggestive of a bleeding disorder

16. Laboratory investigations I Laboratory tests of primary and secondary hemostatic mechanisms are used for two purposes: General screening tests Tests to define specific platelet or clotting factor abnormalities

17. Laboratory investigations II Blood count and film show the number and morphology of platelets The normal range for the platelet count is 150–400×10 9 /L. Coagulation tests are performed using blood collected into citrate, which neutralizes calcium ions and prevents clotting. It involves the following:

18. Laboratory investigations III The prothrombin time ( PT ) is measured by adding tissue factor (thromboplastin) and calcium to the patient’s plasma . The normal PT is 12–16 s when used to measure oral anticoagulants is expressed as the international normalized ratio, INR The PT measures VII, X, V, prothrombin and fibrinogen (classic ‘extrinsic’ pathway) and is prolonged with abnormalities of these factors. It may also be abnormal in liver disease, or if the patient is on warfarin.

19. Laboratory investigations IV The activated partial thromboplastin time ( APTT ) It is performed by adding a surface activator phospholipid (to mimic platelet membrane) and calcium to the patient’s plasma . The normal APTT is 26–37 s The APTT measures XII, XI, IX, VIII, X, V, prothrombin and fibrinogen (classic ‘intrinsic’ pathway) and is prolonged with decencies of one or more of these factors .. The thrombin time ( TT ) is performed by adding thrombin to the patient’s plasma. The normal TT is 12–14 s and it is prolonged with fibrinogen deficiency, qualitative defects of fibrinogen ( dysfibrinogenaemia ) or inhibitors such as heparin or FDPs.

20. Laboratory investigations V Factor assays are used to confirm coagulation defects, especially where a single inherited disorder is suspected. Special tests of coagulation will often be required to confirm the precise hemostatic defect. Such tests include estimation of fibrinogen and FDPs, platelet function tests such as platelet aggregation and platelet granule contents.

21. Laboratory investigations VI Bleeding time measures platelet plug formation in vivo . A sphygmomanometer cuff is in inflated to 40 mmHg, and 1 mm deep, 1 cm long incisions in the forearm are made with a template. Wounds are blotted every 30 s and the time taken for bleeding to stop recorded (normally 3–10 min). Prolonged bleeding times are found in patients with platelet function defects, and there is a progressive prolongation with platelet counts less than 100 × 109/L – hence the bleeding time should not be performed at low platelet counts. Nowadays it is rarely done as it can scar and is painful.

22. Expected results of tests for hemostatic function in representative bleeding disorders Disorder BT Plt PT aPTT TT Vasculopathies Long Normal Normal Normal Normal Thrombocytopenia Long Low Normal Normal Normal Qualitative platelet abnormalities Long Normal or low Normal Normal Normal Hemophilia A (factor VIII deficiency) Normal Normal Normal Long Normal von Willebrand disease Long Normal Normal Long Normal

23. Practice !

24. Case1: A 50-year-old woman, known case of SLE and thyroiditis presents approximately 3 weeks after an upper respiratory tract illness with petechiae , easy bruising, and gum bleeding. She has no personal or family history of a bleeding disorder and takes no medicines. Physical examination is normal except for petechiae and bruising . Specifically, she has no lymphadenopathy or hepatosplenomegaly. FBC reveals thrombocytopenia with a platelet count of 12 x 10^9/L (12 x 10^3/ microlitre ) but other cell lines are within normal limits. Peripheral smear shows thrombocytopenia but no other abnormalities . PT, aPTT , TT are all within normal range.

25. Idiopathic thrombocytopenic purpura Thrombocytopenia is due to the presence of antiplatelet antibodies leading to rapid clearance and immune destruction of platelets. characteristically seen in women associated with other autoimmune disorders such as SLE, thyroid disease and autoimmune haemolytic anaemia (Evans’ syndrome) Platelet autoantibodies are detected in about 60–70% of patients, and are presumed to be present, although not detectable , in the remaining patients. Tx . intravenous immunoglobulin (IVIG) plus corticosteroids

26. Case2: An 18-month-old boy presents with left ankle swelling and pain. He has limited range of motion at the ankle and has difficulty walking. Previous history revealed significant hematomas at immunization sites over the last year. his uncle has a similar condition. Physical examination revealed hemarthrosis and multiple hematomas. Lab investigations revealed prolonged aPTT , clotting factors essays revealed factor VIII deficiency, other blood indices were normal.

27. Hemophilia A: Hemophilia A is a bleeding disorder, with an X-linked recessive inheritance pattern, which results from the deficiency of clotting factor VIII . family history of hemophilia (family history from the maternal side usually positive), and male sex . Typical history includes recurrent or severe bleeding symptoms, or bleeding in unusual sites (e.g., joints or muscles). Minor mucocutaneous bleeding (e.g., epistaxis, bleeding from gums following minor dental procedures, easy bruising ) Tx . Factor VIII concentrate

28. Case 3: A 4-year-old boy presents with a 7-day history of abdominal pain and watery diarrhoea that became bloody after the first day. Three days before the onset of symptoms, he had visited a fairground with his family and had eaten a burger . Physical examination reveals a pallor and signs of dehydration. Investigations revealed the following: low Hg, thrombocytopenia, shistocytes on PBS, stool culture was positive for ECEC.

29. Hemolytic uremic syndrome It occurs most commonly in children 1-5 y/o. Characterized by : acute pallor, uremia and diarrhea or dysentery. The anemia develops 5-10 following the diarrhea attack. There usually a history of ingestion of food that may have been contaminated with E coli, or a community outbreak. Tx . I.v. crystalloid, RBC transfusion

30. References: Kumar and Clark’s: Clinical Medicine, 8 th edition UpToDate : Approach to the adult patient with a bleeding diathesis. B leeding disorders: diagnostic approach simplified Susan G. Hackner , BVSc.MRCVS.DACVIM . DACVECC. BMJ: Hemophilia BMJ : ITP

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