Clinical assessment, pertinent history, and family history are good indicators for determining patient's bleeding tendencies. The most appropriate laboratory tests performed are Routine screening tests include a complete blood cell count, platelet count, and evaluation of a peripheral blood sample, a prothrombin time, and an activated partial thromboplastin time.

1. Good
Morning

2. Presented by:
Dr.Prashant Munde
( MDS- I )
Guided by :
Dr. Mrs. SHUBHANGI KHANDEKAR
( PROFESSOR & GUIDE )
Dr. Mrs. ALKA DIVE
( PROFESSOR & H.O.D)

3. Hemorrhagic Disorders
 Hemorrhagic or Bleeding disorders are a group of
conditions in which there is a problem with the body's
blood clotting process.
 These disorders can lead to heavy and prolonged bleeding
after an injury. Bleeding can also begin on its own.
 Defects in blood coagulation usually give abnormal
coagulation tests and C.T.

4. Causes
 Normal blood clotting involves coagulation factors
which act together with other chemicals to form
fibrin that stops bleeding.
 Problems can occur when certain coagulation
factors are low or missing.
 Bleeding disorders can also result from having
poorly working or too few platelets.

5.  Some bleeding disorders are present at birth and
are passed through families (inherited).
Others develop from:
 Illnesses such as vitamin K deficiency or severe
liver disease.
 Treatments such as the use of drugs to stop blood
clots (anticoagulants) or the long-term use of
antibiotics.

6. Diagnosis of Hemorrhagic Disorders
Present history: Rash following infection, abdominal and
joint pain.
Family History: For evidence of inheritance of any
bleeding tendencies.
Past History: Excessive, prolonged bleeding of the
surgical interventions as tonsillectomy, circumcision
or tooth extraction.
Physical Examination: General condition, type and
distribution of the rash, fever, organ enlargement,
lymph glands.

7. Hemorrhagic disorders
Excessive bleeding can result from
(1) Increased fragility of vessels,
(2) Platelet deficiency or dysfunction, and
(3) Derangement of coagulation, alone or in combination.
 Common laboratory tests used in the evaluation of a bleeding
disorders are the following:

8. Screening tests:
 Bleeding Time
 Complete blood count (CBC)
 Prothrombin Time
 Activated partial thromboplastin time
 Thrombin Time
 Fibrinogen activity test
Tests of Hemorrhagic Disorders

9. BLEEDING TIME

10. Bleeding time
oBleeding time - The time when the incision is made until all
bleeding has stopped is measured and is called the bleeding time.
o Used to assess platelet function.
oA prolonged bleeding time may be a result from decreased
number of thrombocytes or impaired blood vessels.
o However, the depth of the puncture or incision may be the
source of error.

11. Methods
Duke Method
o With the Duke method, the patient is pricked with a needle or
lancet, on fingertip, after swabbed with alcohol.
o The prick is about 3–4 mm deep.
o Every 30 seconds, filter paper or a paper towel is used to
wipes the blood .
o Normal values- is about 2–5 minutes.

12. Ivy method
 In the Ivy method, the blood pressure cuff is placed on
upper arm and inflated to 40 mmHg.
 A lancet is used to make a shallow incision on the
underside of the forearm.
 Every 30 seconds, filter paper or a paper towel is used to
draw off the blood.
 Normal values - 3 – 10 minutes

13. Interpretation
 Bleeding time is affected by platelet function, certain vascular
disorders and von Willebrand Disease—not by other coagulation
factors such as hemophilia.
 Diseases that cause prolonged bleeding time include
 Thrombocytopenia,
 Disorders of platelet function
 Disseminated intravascular coagulation (DIC),
 Acute Leukemia
 Aplastic anemia
 Liver diseases

14.  Aspirin and other cyclooxygenase inhibitors can prolong
bleeding time significantly.
 While warfarin and heparin have their major effects on
coagulation factors, an increased bleeding time.
 People with von Willebrand disease usually experience
increased bleeding time, as von Willebrand factor is a
platelet adhesion protein, but this is not considered an
effective diagnostic test for this condition.

15. Complete blood count (CBC)

16. Complete blood count (CBC)
 RBC count
 WBC count
 The total amount of hemoglobin in the blood
 The fraction of the blood composed of red blood cells (hematocrit)
 The platelet count.
The CBC test also provides information about:
 Average red blood cell size (MCV)
 Hemoglobin amount per red blood cell (MCH)
 The amount of hemoglobin relative to the size of cell (hemoglobin
concentration) per red blood cell (MCHC).

17.  A complete blood count (CBC) is used to detect or monitor many
different health conditions.
 Diagnose infections or allergies
 Detect blood clotting problems or blood disorders, including
anemia.
 Evaluate red blood cell production or destruction.
 The CBC interpretation are useful in the diagnosis of various
types of anemias.
 It can reflect acute or chronic infection, allergies, and problems
with blood clotting.

18. Normal Results
Blood counts may vary with altitude. In general, normal
results are:
 RBC count:
 Male: 4.7 to 6.1 million cells/mcL
 Female: 4.2 to 5.4 million cells/mcL
 WBC count:
 4,500 to 10,000 cells/mcL
 Hematocrit:
 Male: 40.7 to 50.3%
 Female: 36.1 to 44.3%

19. Hemoglobin:
 Male: 13.8 to 17.2 gm/dL
 Female: 12.1 to 15.1 gm/dL
Red blood cell indices:
 MCV: 80 to 95 femtoliter
 MCH: 27 to 31 pg/cell
 MCHC: 32 to 36 gm/dL

20. Abnormal Results
A high RBC or hematocrit may be due to:
 Dehydration (such as from severe diarrhea)
 Kidney disease with high erythropoietin production
 Low oxygen level in the blood for a long time due to
heart or lung disease.
 Polycythemia vera

21. A low RBC or hematacrit is a sign of anemia, which can result from:
 Autoimmune diseases ( lupus erythematosus or rheumatoid arthritis)
 Blood loss (hemorrhage)
 Bone marrow failure ( from radiation, infection, or tumor)
 Chronic kidney disease
 Hemolysis (red blood cell destruction)
 Leukemia and other blood cancers
 Long-term infections such as hepatitis
 Poor diet and nutrition, causing too little iron, folate, vitamin B12, or
vitamin B6

22. A lower than normal white blood cell count is called
leucopenia.
A decreased WBC count may be due to:
 Autoimmune diseases (such as systemic lupus
erythematosus)
 Bone marrow failure (for example, due to infection,
tumor, radiation, or fibrosis)
 Disease of the liver or spleen

23. High numbers of WBCs is called leukocytosis.
It can result from:
 Infectious diseases
 Inflammatory disease (such as rheumatoid
arthritis or allergy)
 Leukemia
 Severe emotional or physical stress
 Tissue damage (such as burns)

24.  A complete blood count with differential WBC Count will
also include:
 Neutrophil — May indicate bacterial infection.
 May also be raised in acute viral infections.
 Eosinophilic — Increased in parasitic infections, asthma,
or allergic reaction.

25.  Basophil — May be increased in bone marrow related conditions
such as leukemia or lymphoma.
 Lymphocytes — Higher with some viral infections such as
glandular fever and raised in chronic lymphocytic leukemia (CLL).
Can be decreased by HIV infection.
 Monocytes — May be raised in bacterial infection, tuberculosis,
malaria, Rocky Mountain spotted fever, monocytic leukemia,
chronic ulcerative colitis and regional enteritis .

26. Platelet counts
These are obtained on anticoagulated blood using an electronic
particle counter.
The reference range is 1.5 to 4 lac platelets/mm3.
Bleeding resulting from thrombocytopenia is associated with a
normal PT and PTT.
NORMAL 100,000 - 400,000 Cells/mm3
< 100,000 Thrombocytopenia
50,000 - 100,000 Mild Thrombocytopenia
< 20,000 SevereThrombocytopenia Spontaneous bleeding
Bleed after major trauma
Bleed after minor trauma

27. Counts well outside this range should be confirmed by a
visual inspection of a peripheral blood smear, since
clumping of platelets can cause “thrombocytopenia”
during automated counting, and high counts may be
indicative of a myeloproliferative disorder, such as
essential thrombocythemia.

28.  Increase platelet counts can be due to :
 Essential (primary)
 Essential thrombocytosis (a form of myeloproliferative
disease)
 Other myeloproliferative disorders such as chronic
myelogenous leukemia, polycythemia vera, myelofibrosis
 It manifests clinically with elevated platelet counts and is
separated from PCV and primary myelofibrosis based on the
absence of polycythemia and marrow fibrosis, respectively. In
those cases without tyrosine kinase mutations, causes of reactive
 thrombocytosis, such as inflammatory disorders and iron
deficiency, must be excluded before the diagnosis can be
established.

29.  Reactive (secondary)
 Inflammation
 Surgery (which leads to an inflammatory state)
 Hyposplenism (decreased breakdown due to decreased
function of the spleen)
 Splenectomy
 Iron deficiency anemia or hemorrhage

30. Decreased platelet counts can be due to
 Idiopathic thrombocytopenic purpura
 Thrombotic thrombocytopenic purpura
 Disseminated intravascular coagulation
 Systemic lupus erythematosus
 Vitamin B12 or folic acid deficiency
 Leukemia or myelodysplastic syndrome
 Sepsis, systemic viral or bacterial infection
 chemotherapy drugs
 Valproic acid, Methotrexate, Interferon,Isotretinoin

31. Tests of platelet function
At present, no single test provides an adequate
assessment of the complex functions of platelets.
One older test, the bleeding time, which measures the time
taken for a standardized skin puncture to stop bleeding,
has some value but is time-consuming, difficult to perform
well, and not a good predictor of bleeding during
haemostatic stresses such as surgery.
As a result of these limitations, the use of the bleeding time
has declined considerably in recent years.

32. Newer instrument-based assays designed to measure platelet
function under conditions of high shear stress show promise
but at present are also less than ideal screening tests.
Other specialized tests that can be useful in particular clinical
settings include
Tests of platelet aggregation, which measure the ability of
platelets to aggregate in response to agonists like thrombin;
and quantitative and qualitative tests of von Willebrand
factor, which play an important role in platelet adhesion to
the extracellular matrix.

33.  More specialized tests are available to
measure the levels of specific clotting
factors, fibrinogen, fibrin split products, and
the presence of circulating anticoagulants.

34. Tests of blood coagulation

35.  Routine tests of blood coagulation, such as the
 Prothrombin time (PT),
 Activated partial thromboplastin time (aPTT), and
 Thrombin time (TT)
are frequently ordered to assess clotting function in
patients.

36. Prothrombin time (PT)

37. oThe prothrombin time is the time it takes plasma to clot after
addition of tissue factor.
oThis measures the quality of the extrinsic pathway (as well as
the common pathway) of coagulation.
oThey are used to determine the clotting tendency of blood, in
the measure of warfarin dosage, liver damage, and vitamin K
status.
Prothrombin time (PT)

38. oPT measures factors I (fibrinogen), II (prothrombin),
V, VII, and X.
o It is used in conjunction with the activated partial
thromboplastin time (aPTT) which measures the intrinsic
pathway.
oNormal range
oThe reference range for prothrombin time is usually
around 12-13 seconds, and the INR in absence of
anticoagulation therapy is 0.8-1.2.

39. Interpretation
•The prothrombin time can be prolonged as a result of
Deficiencies in vitamin K,
• warfarin therapy,
•Malabsorption, or lack of intestinal colonization by
bacteria (such as in newborns).
•Poor factor VII synthesis (due to liver disease) or
•Increased consumption (in disseminated intravascular
coagulation) may prolong the PT.

40. •The INR is typically used to monitor patients on warfarin
or related oral anticoagulant therapy.
•The normal range of INR for a healthy person not using
warfarin is 0.8–1.2 sec., and for people on warfarin therapy
2 –3 sec.
•High INR indicates a higher risk of bleeding, while a low
INR suggests a higher risk of developing a clot.

41. Activated partial
thromboplastin time (APTT)

42. oThe partial thromboplastin time (PTT) or activated partial
thromboplastin time (aPTT or APTT) test assesses both the
intrinsic and common clotting pathways.
The clotting of plasma after addition of kaolin, cephalin, and Ca [2]
+ ions is measured in seconds.
Kaolin activates the contact dependent factor XII, and cephalin
substitutes for platelet phospholipids.
ACTIVATED PARTIAL THROMBOPLASTIN TIME

43. oApart from detecting abnormalities in blood clotting,it is
also used to monitor the treatment effects with heparin, a
major anticoagulant. It is used in conjunction with the
prothrombin time (PT) which measures the extrinsic pathway.
o Prolongation of the PTT can be due to deficiency or
dysfunction of factors V, VIII, IX, X, XI, or XII,
prothrombin, or fibrinogen.

44. •Interpretation
•The typical reference range is between 30 seconds and 50 s.
•Shortening of the PTT is considered to have little clinical
relevance, but it might increase risk of thromboembolism.
•Normal PTT times require the presence of coagulation factors:
• I, II, V, VIII, IX, X, XI, & XII.
•Deficiencies in factors VII or XIII will not be detected with
PTT test.

45. •Prolonged APTT may indicate:
•use of heparin (or contamination of the sample)
•Antiphospholipid antibody (especially lupus anticoagulant,
which paradoxically increases propensity to thrombosis)
•coagulation factor deficiency (e.g. hemophilia)
•Sepsis - coagulation factor consumption
•Presence of antibodies against coagulation factors
(Factor inhibitors)

46. Mixing test
Patient plasma
Normal plasma
PTT
Correctable PTT Factor deficiency
• If the abnormality does not disappear, the sample is said to contain
an "inhibitor" (either heparin, antiphospholipid antibodies or
coagulation factor specific inhibitors), while if it does correct a
factor deficiency is more likely.

47. THROMBIN TIME

48. •The thrombin time (TT), measures the time it takes for a
clot to form in the plasma of a blood sample containing
anticoagulant, after an excess of thrombin has been added.
•It is used to diagnose blood coagulation disorders and to
assess the effectiveness of fibrinolytic therapy.
•This test is repeated with pooled plasma from normal
patients.
Thrombin time

49. •The difference in time between the test and the 'normal'
indicates an abnormality in the conversion of fibrinogen to
fibrin.
•Normal values for thrombin time are 12 to 14 seconds.
•Thrombin time can be prolonged by heparin, fibrin
degradation products, factor XIII deficiency, and
fibrinogen deficiency or abnormality.

50. FIBRINOGEN ACTIVITY
TEST

51. A fibrinogen activity test is ordered as part of an
investigation of a possible bleeding disorder or
thrombotic episode.
It may be ordered as a follow-up to an abnormal
Prothrombin Time (PT) or Partial Thromboplastin Time
(PTT) and/or an episode of prolonged or unexplained
bleeding.
FIBRINOGEN ACTIVITY TEST

52. •It may be measured, along with tests such as PT, PTT, platelet
function tests, fibrin degradation products (FDP), and D-dimer
to help diagnose disseminated intravascular coagulation (DIC)
or abnormal fibrinolysis.
•Fibrinogen activity test is ordered to help monitor the status
of a progressive disease (such as liver disease) over time.
•Sometimes this test is ordered, along with other cardiac risk
markers such as C-reactive protein (CRP), to help determine a
person's overall risk of developing cardiovascular disease.

53. • Fibrinogen levels can be measured in venous blood.
• Normal levels are about 1.5-3 g/L, depending on the
method used.
• Higher levels are, amongst others, associated with
cardiovascular disease (>3.43 g/L).
• It may be elevated in any form of inflammation, as it is
an acute-phase protein; for example, it is especially
apparent in human gingival tissue during the initial phase
of periodontal disease.

54. •Low levels of fibrinogen can indicate a systemic activation
of the clotting system, with consumption of clotting
factors faster than synthesis.
• This excessive clotting factor consumption condition is
known as disseminated intravascular coagulation or "DIC.“
• In DIC low fibrinogen levels with prolonged clotting
times (PT or aPTT), in the context of acute critical illness
such as sepsis or trauma.

55.  Fibrinogen levels are increased in:
 Increasing age
Female sex, pregnancy, oral contraception
In post-menopausal women
Acute phase reaction
Disseminated malignancy

56. Fibrinogen levels are reduced in:
DIC due the the consumption of clotting factors.
Liver disease due to decreased synthesis.
Massive transfusion
Inherited deficiencies e.g. Hypofibrinogenaemia, afibrinogenaemia
and dysfibrinogenaemia
Following thrombolytic therapy
In some patients following treatment with asparaginase

57. FACTOR ASSAYS TESTS

58.  Clotting Factor Tests
 Clotting factor tests, also called factor assays, are
required to diagnose a bleeding disorder.
 This blood test shows the type of hemophilia and the
severity.
 It is important to know the type and severity in order
to create the best treatment plan.

59. Haemophilia A and Haemophilia B:
 Activated partial thromboplastin time (APTT);
prolongation depends on the severity of the factor
deficiency.
 Prolonged APTT plus prolonged bleeding suggests von
Willebrand's disease
 factor VIII clotting assay - low levels in Haemophilia A
 factor IX clotting assay - low levels in Haemophilia B
 In severe cases of Haemophilia B whole blood
coagulation time is increased

60.  The severity of vWD varies and many patients will never be
diagnosed, as their disorder may never come to light.
 In practice - both primary and secondary - the patients
with more severe forms of the disorder will present with
abnormal bleeding.
 Following this, basic blood tests including FBC, clotting
screen and liver function should be performed and patients
should be referred for a specialist opinion and other more
specialised investigations such as plasma levels of vWf.

61.  Plasma levels of vWF – Deficiency can be quantitative
or qualitative.
 Quantitative deficiency - detected by vWF antigen assay.
 Qualitative deficiency - detected by a number of methods
including glycoprotein binding assay, ristocetin cofactor
activity, ristocetin-induced platelet agglutination.

62.  Factor VIII measurement:
 Factor VIII binds to vWF which in turn prevents the rapid
breakdown of factor VIII; thus, a deficiency of vWF can also
lead to deficiency of factor VIII.
 In type 2 vWF - factor VIII levels are normal; studies of
platelet aggregation with sub-endothelium are necessary.
 Oestrogens, vasopressin and growth hormone all elevate
levels.

63.  These include assays of factor VIII, von Willebrand factor
antigen, von Willebrand factor activity (measured by the
ristocetin cofactor assay), and template bleeding time. In von
Willebrand disease the defect is in von Willebrand factor.
 The affected individual may have subnormal levels of
structurally and functionally normal von Willebrand factor (this
is called "classic" or type I von Willebrand disease) or may
produce von Willebrand factor that is structurally and
functionally abnormal (von Willebrand disease type 2).

64.  Individuals who inherit a gene for von Willebrand
disease from both parents have severe (type 3) von
Willebrand disease and will have extremely low levels
(< 3%) of von Willebrand factor and factor VIII and
will have a very prolonged bleeding time.
 In most populations type I disease is the most
common form, whereas type 3 is the least commonly
encountered form.
 It should be noted that levels of von Willebrand
factor can be influenced by the patient's blood type
(persons who have blood type AB have 60% to 70%
higher levels than do persons who have blood type O)
and can be elevated during pregnancy, stress, and
hyperthyroidism.

65. Disseminated intravascular coagulation
 Diagnosis is usually suggested by-
 Severe cases with hemorrhage:
 The PT and APTT are usually very prolonged and the fibrinogen
level markedly reduced.
 High levels of fibrin degradation products, including D-dimer.

66.  There is severe thrombocytopenia.
 The blood film may show fragmented red blood cells
(schistocytes).
 Mild cases without bleeding:
 There is increased synthesis of coagulation factors and
platelets.
 PT, APTT, and platelet counts are normal.
 Fibrin degradation products are raised.

67.  Clinical assessment, pertinent history, and family
history are good indicators for determining patient's
bleeding tendencies.
 The most appropriate laboratory tests performed are
Routine screening tests include a complete blood cell
count, platelet count, and evaluation of a peripheral
blood sample, a prothrombin time, and an activated
partial thromboplastin time.
Summary

68. References
 Kumar, V., & Robbins, S. L. 1. (2007). Robbins basic pathology (8th ed.).
Philadelphia, PA: Saunders/Elsevier.
 Hoffman Hematology: Basic Principles and Practice. 5th ed. Philadelphia,
Pa: Churchill Livingstone Elsevier; 2008:chap 121.
 Kessler C. Hemorrhagic disorders: Coagulation factor deficiencies. In:
Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa:
Saunders Elsevier;2007:chap 180.
 Hoffbrand AV, Pettitt JE (1999). Essential Haematology. Blackwell
Scientific Publications, Oxford.