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

1. Approach 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:
Primary
hemostasis
Secondary
hemostasis
Fibrinolysis

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:
1. Is the bleeding due to local factors, or a generalized bleeding
disorder?
2. Is the defect congenital or acquired?
3. If a systemic disorder does exist, what is the nature of the
hemostatic defect? “ Vascular/platelet defect (primary hemostasis)
or coagulation defect (secondary hemostasis) “

11. History Examination
investigations

12. History I
• Is there a generalized hemostatic defect?
bleeding
from
multiple sites
spontaneous
bleeding
excessive
bleeding
after injury

13. 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.

14. 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.

15. 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.

16. 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.
skin
mucus
membranes
Joints eyes
Urine and
feces
liver and
spleen
lymph
nodes
The presence of hemorrhage in more than one site is suggestive of a bleeding
disorder

17. 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

18. Laboratory investigations II
• Blood count and film
 show the number and morphology of platelets
 The normal range for the platelet count is 150–400×109/L.
• Coagulation tests are performed using blood collected into citrate,
which neutralizes calcium ions and prevents clotting.
• It involves the following:

19. 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.

20. 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.

21. 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.

22. 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.

23. 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

24. Practice !

25. 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.

26. 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

27. 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.

28. 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

29. 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.

30. 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

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

32. Thank you for listening