This document discusses hemostasis and blood transfusion. It begins with definitions of hemostasis and describes the five stages of hemostasis: vascular phase, platelet phase, coagulation phase, clot retraction, and fibrinolysis. It then discusses investigations for disorders of hemostasis, including clinical evaluation and laboratory tests. Major disorders of hemostasis are outlined, including inherited and acquired issues with blood vessels, platelets, and coagulation. The document also covers blood components, indications for component therapy, and potential complications of blood transfusion.

1. HEMOSTASIS
&
BLOOD TRANSFUSION
By
Dr. Abdul Qadeer Memon
MBBS; FCPS; FICS
Assistant Professor in General Surgery
King Faisal University College of Medicine
Kingdom of Saudi Arabia

2. OBJECTIVES
1. Definition of hemostatsis
2. Mechanism of hemostasis
3. Investigations for disorders of hemostasis
4. Major disorders of hemostasis
5. Blood components
6. Indications for component therapy
7. Complications of blood transfusion

3. 1. DEFINITION OF HEMOSTATSIS
 Heme = Blood + Stasis = To halt
(Stop)
 It is the process of forming clots in the wall
of damaged blood vessels & preventing
blood loss while maintaining blood in a
fluid state within the vascular system.
 Spontaneous arrest of bleeding by
physiological process.

5. MAINTAINS BLOOD FLOW
PREVENTS BLOOD
LOSS

6. 2. MECHANISM OF HEMOSTASIS
 Hemostasis consists of the following steps
a. Vascular Phase
b. Platelet Phase
c. Coagulation Phase (Clot formation)
d. Clot retraction
e. Fibrinolysis

7. STAGES OF HEMOSTASIS

8. STAGES OF HEMOSTASIS

9. A) VASCULAR PHASE OF HEMOSTATSIS

10. VASCULAR PHASE OF HEMOSTATSIS

11. B) PLATELET PHASE

12. PLATELET PHASE (PLATELET PLUG)

14. C) COAGULATION PHASE (BLOOD CLOT)

17. D) CLOT RETRACTION
 Release of fibrin stabilizing factor
 Contractile protein of platelets
 Activated and accelerated by thrombin and
Ca+2 ions.

18. E) FIBRINOLYSIS

19. ?

20. 3. INVESTIGATIONS FOR DISORDERS OF
HEMOSTASIS
 The approach towards the diagnosis:
a. Clinical Evaluation
History
Physical Examination
Family history
b. Laboratory Evaluation
Screening test
Specific test

21. CLINICAL FEATURES IN THE DISORDERS OF
HEMOSTASIS
Clinical feature Platelet
disorder
Coagulation
disorder
Site of bleeding Skin
(epistaxis, gum,
vaginal, GI tract)
Deep in soft tissues
Mucous membranes,
joints, muscles)
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,
Usually mild
Delayed (1-2 days),
Often severe

22. PLATELET COAGULATION
PETECHIAE, PURPURA HEMATOMA, JOINT BL.

23. TESTS FOR PRIMARY HEMOSTASIS I.E PLATELET-MEDIATED
COAGULATION
 Bleeding time Platelet & vascular phases
 PFA – 100 system Platelet function
 Platelet count Quantification of platelets
 Blood smear Quantitative &
morphological
abnormalities of platelets ,
Detection of underlying
haemotological disorder

24. TESTS FOR SECONDARY HEMOSTASIS I.E
PLASMA PROTEIN-MEDIATED COAGULATION
 Clotting time Crude test of coagulation
phase
 Prothrombin time Extrensic & common
pathway
 Activated partial
thromboplastin time Intrinsic & common pathway

25. OTHER TESTS FOR HEMOSTASIS
 Thrombin time
 INR = International Normalized Ratio

26. PLATELET COUNT
NORMAL 150,000 - 400,000
Cells/mm3
< 100,000 Thrombocytopenia
50,000 - 100,000 Mild Thrombocytopenia
< 50,000 Severe Thrombocytopenia

27. BLEEDING TIME (BT)
The duration of bleeding after controlled,
standardized puncture of the earlobe or forearm
Provides assessment of platelet count and
function
Normal value
2-8 minutes

28. CLOTTING (COAGULATION) TIME (CT)
 The time required for blood to clot in a glass
tube
Normal value
5-15 Min

29. PROTHROMBIN TIME (PT)
 The rate at which prothrombin is converted to
thrombin in citrated blood with added calcium;
 Measures Effectiveness of the Extrinsic
Pathway
Measures the activity of V, VII, X, II , I
Normal value
11-16 Sec

30. ACTIVATED PARTIAL THROMBOPLASTIN
TIME (APTT)
 Period required for clot formation in re-calcified
blood plasma after contact activation
& addition of platelet substitutes.
It measures effectiveness of
Intrinsic pathway &
common pathway
Normal value
25-40 Sec

31. THROMBIN TIME (TT)
 Time for Thrombin To Convert Fibrinogen into
Fibrin
 A Measure of Fibrinolytic Pathway
Normal value
9-13 sec

32. INR (INTERNATIONAL NORMALOIZED RATIO)
 It is a laboratory measurement of how long it takes
blood to form a clot. It is used to determine the
effects of oral anticoagulants (e.g. Warfarin /
Coudamin) on the clotting system.
 All PT results are standardized by this calculation:
 INR= ( Patient PT / Control PT)
ISI
 ISI= International sensitivity index, Given by the manufacturer for each
particular thromboplastin reagent and instrument combination

33. SIGNIFICANCE OF INR

34. SPECIFIC TESTS
 Tests for specific Platelet Functions
1. Platelet aggregation test
2. Flow cytometry
3. Test for platelet secretion
4. Clot retraction test
5. Platelet procoagulant activity
 Test for Coagulation Phase
1. Quantitative estimation of Fibrinogen
2. Coagulation factor assays
3. F XIII Qualitative assay
 Latex agglutination test for Fibrinolysis

35. ?

36. 4. MAJOR DISORDERS OF HEMOSTASIS
INHERITED
 Vascular
 Platelet
 Coagulation
 Fibrinolytic
ACQUIRED
 Vascular
 Platelet
 Coagulation

37. HEMORRHAGIC DISORDERS
 Hemorrhagic disorders are characterized by
a disorder of one or more factors that
participate in hemostasis. The majority of
hemorrhagic syndromes are blood vessel
disorders, platelet number and function
disorders, or coagulation factor disorders:
a. vasculopathies
b. thrombocytopenias
c. thrombocytopathies
d. coagulopathies.

38. VASCULOPATHIES
 Vasculopathies may be inherited or acquired.
 Inherited forms result from blood vessel
structure disorders (inherited telangiectasia,
Rendu-Osler-Weber’s disease) while acquired
disorders can be a consequence of
inflammatory or immune processes that damage
blood vessel walls.
 In clinical practice, acquired disorders are
found more frequently (secondary purpuras,
infections,
effects of some drugs, allergic purpura, effect of
aspirin, vitamin C deficiency, etc.).

39. THROMBOCYTOPENIAS
 Thrombocytopenia, or reduced circulating platelet count,
can be inherited or acquired; the acquired form being more
frequent.
 Thrombocytopenia occurs as a result of:
– decreased platelet formation with normal platelet
survival time (effects of irradiation, drugs, malignant tissue
pressure on bone marrow, leukemias, aplastic anemias) or
− increased platelet degradation or platelet deposit in
spleen with decreased platelet survival (DIC, effects of
drugs, bacterial or viral infections, inherited idiopathic
thrombocytopenic purpura, chronic leukemias, lupus
erythematosus,Hodgkin’s disease, massive transfusions
and liver cirrhosis).

40. THROMBOCYTOPATHIES
 Inherited Qualitative Platelet Disorders may be due
to abnormalities of
1. platelet membrane glycoproteins,
- Glanzmann Thrombastenia, abnormal GPIIb/IIIa
– Bernard-Soulier Syndrome, abnormal GPIb, GPIX and
GPV
– platelet-type of vWD, abnormal GPIb
2. platelet granules,
 These may occur due to absence of granules in
platelets, storage pool disorder (characterized by
disturbed platelet aggregation to collagen, adrenaline
and thrombin), or disturbed release (absence of T A2).

41. THROMBOCYTOPATHIES (CONTD.)
3. platelet coagulant activity, or
4. signal transduction and secretion.
 defects in arachidonic acid metabolism,
 cyclooxigenase deficiency, platelets unable to produce
thromboxane; endothelium may not produce
prostacyclin,
 thromboxane synthesis deficiency, and
 defects in platelet secretion and the second wave of
platelet aggregation, found in response to epinephrine
or ATP.

42. COAGULOPATHIES

43. ACQUIRED BLOOD CLOTTING DISORDERS
They occur in:
 Vitamin K deficiency,
 Liver diseases,
 Liver transplantation,
 Disseminated intravascular coagulation,
 Renal diseases,
 Primary pathological fibrinolysis
 During the course of anticoagulant therapy.

44. ?

45. 5. BLOOD COMPONENTS

46. BLOOD COMPONENTS (%)

47. BLOOD COMPONENTS
 Many blood components and its products are
being used in clinical practice.
 These can be classified as:
A. Related to erythrocytes
B. Related to platelets
C. Related to leucocytes
D. Related to plasma
E. Related to serum
F. Artificial blood
G. Others

48. A. BLOOD PRODUCTS RELATED TO
ERYTHROCYTES
 These include:
i. Whole blood
ii. Packed red cells
iii. WBC poor red cells
iv. Washed red cells
v. Frozen red cells

49. B. BLOOD PRODUCTS RELATED TO PLATELETS
 These include:
i. Platelet rich plasma
ii. Platelet concentrate
iii. Frozen platelets

50. C. BLOOD PRODUCTS RELATED TO LEUCOCYTES
 These include:
i. Granulocyte rich plasma
ii. Lymphocyte rich plasma

51. D. BLOOD PRODUCTS RELATED TO PLASMA
 These include:
i. Fresh plasma
ii. Fresh frozen plasma (FFP)
iii. Freeze dried plasma
iv. Cryoprecipitate
v. Prothrombin complex
vi. Coagulation factors concentrates
vii. Antithrombin III
viii. Fibrinogen
ix. Protein C & S

52. E. BLOOD PRODUCTS RELATED TO SERUM
 These include:
i. Normal pool serum
ii. Freeze dried serum
iii. Serum immune globulin
iv. Normal serum albumin

53. F. BLOOD PRODUCTS RELATED TO ARTIFICIAL
BLOOD
 Theses include red cell substitutes

54. G. BLOOD PRODUCTS RELATED TO PLASMA
SUBSTITUTE
 This includes 6% Dextran solution

55. ?

56. 6. INDICATIONS FOR COMPONENT THERAPY

57. WHOLE BLOOD
 Used in hypovlemia due to blood loss
 Disadvantages:
i. If not screened properly, can cause hepatitis
ii. Allergic & febrile reactions
iii. Stored blood may increases level of K+
iv. It is devoid of platelets & clotting factors

58. PACKED RED BLOOD CELLS
 Given to the patients with anemia and blood
loss
 One unit of PRBCs will raise Hb level of 1.5
gm/dl
 Does not provide platelets
and clotting factors

59. WASHED RED CELLS
 Antibodies in donor serum is eliminated if
cross-matching shows minor positive
 Desirable to transfer to the patient of
paroxysmal nocturnal hemoglobinuria
 It also does not provide platelets and clotting
factors

60. LEUKOCYTE-POOR RED CELLS
 Given to the patients such as
 With high titer leukocyte antibodies
 Who have or had repeated febrile transfusion
reactions
 With organ transplantation e.g. B.M, kidney

61. FROZEN RED CELLS
 Frozen red cells in glycerol citrate solution
can be stored up to 2 years
 Useful when rare groups are required fro
transfusion
 Disadvantages:
i. Higher cost for this product
ii. Time consuming
iii. Frozen red cells after thawing must be used
within 24 hours because of the possible risk
of bacterial contamination

62. GRANULOCYTE-RICH PLASMA TRANSFUSION
 Given to patients suffering from more than
101oF and having evidence of infection with
positive blood culture
 In case of neutropenia when granulocyte
count < 500 μL
 Lymphocyte-rich plasma may be give to the
patients with lymphocytopenia

63. PLATELET CONCENTRATE
 Can be given in:
a. Marrow aplasia
b. Platelet dysfunction e.g. thromboasthenia
c. Bone marrow and organ transplantation
d. Post-op bleeding when count falls below
25x109/L
e. Cardiac bypass & massive blood transfusion

64.  Disadvantages:
 Platelets transfusion is not indicated in;
a. ITP
b. Drug induced thrombocytopenia
c. Extrinsic platelet dysfunction e.g. vWD and
uremia

65. FRESH FROZEN PLASMA (FFP)
 Can be used in patients with:
 Coagulation factors deficiency
 Hypovolemia
 Shock, acute hemorrhage, plasma loss e.g.
in burns

66. CRYOPRECIPITATE/FACTOR VIII CONCENTRATE
 Used in hemophilia or vWD

67. PROTHROMBIN COMPLEX
 It contains vitamin K-dependent factors i.e. II,
VII, IX & X
 Can be given in the patients having
deficiency of the above factors
 Disadvantages:
 Carries a high risk of transmitting hepatitis
because it is derived from large pool of
donors
 May also cause thrombotic tendency if given
repeatedly

68. IMMUNE SERUM GLOBULIN (GAMMA GLOBULIN)
 Prepared by fractionation of pooled normal
serum or plasma
 Can be used in viral infections e.g. hepatitis
 Can be used in patients with
agammaglobulinemia or
hypogammaglobulinemia

69. SERUM ALBUMIN
 Prepared by the fractionation of pooled
plasma
 Available in 5% and 25%
 Uses:
a. To maintain blood volume
b. Hypoprteinemia

70. ARTIFICIAL BLOOD RELATED TO RED
BLOOD CELL SUBSTITUTES
 Perflouro carbon
 Stroma free hemoglobin

71. 6% DEXTRAN SOLUTION
 Related to plasma substitutes e.g.
i. Intradex
ii. Dextraven
iii. SAG-M
iv. Ad-sol

72. ?

73. 7. COMPLICATIONS OF BLOOD TRANSFUSION
 These include:
I. Transfusion reactions; hemolytic & non-hemolytic
II. Allergic reactions
III. Volume overload
IV. Transfusion related acute lung injury
(TRALI)
V. Graft-vs-host disease (GVHD)
VI. Complications of massive transfusion
VII. Transmission of infections

74. I. TRANSFUSION REACTIONS
 Febrile non-hemolytic & chill-rigor reactions
 Hemolytic reactions due to ABO
incompatibility
 The most common symptoms are chills,
rigors, fever, dyspnea, light-headedness,
urticaria, itching, and flank pain.

75. I. TRANSUSION REACTIONS
WHAT TO DO?
 Prompt reporting to blood bank
 Stop transfusion immediately
 Continue I/V fluids e.g. N. saline

76. II. ALLERGIC REACTIONS
 Due to presence of allergens within the
donor blood
 These reactions are usually mild, with
urticaria, edema, occasional dizziness, and
headache during or immediately after the
transfusion
 Simultaneous fever is common

77. III. VOLUME OVERLOAD
 May be dangerous in the patients with
cardiac failure or renal insufficiency
 The patient should be observed and, if signs
of heart failure (e.g. dyspnea, rales) occur,
the transfusion should be stopped and
treatment for heart failure begun.

78. IV. TRALI
 It is caused by anti-HLA and/or anti-granulocyte
antibodies in donor plasma that
agglutinate and degranulate recipient
granulocytes within the lung.
 Acute respiratory symptoms develop
 Chest x-ray has a characteristic pattern of
non-cardiogenic pulmonary edema.

79. V. GRAFT-VS-HOST DISEASE (GVHD)
 Transfusion-associated GVHD is usually
caused by transfusion of products containing
immunocompetent lymphocytes to an
immunocompromised host.
 The donor lymphocytes attack host tissues.

80. GRAFT-VS-HOST DISEASE (GVHD)
 Symptoms and signs include fever, skin rash
 Vomiting, watery and bloody diarrhea,
lymphadenopathy, and pancytopenia due to
bone marrow aplasia.
 Jaundice and elevated liver enzymes are
also common.
 GVHD occurs 4 to 30 days after transfusion
and is diagnosed based on clinical suspicion
and skin and bone marrow biopsies.
 GVHD has > 90% mortality because no
specific treatment is available.

81. VI. COMPLICATIONS OF MASSIVE TRANSFUSION
 Massive transfusion is transfusion of a
volume of blood greater than or equal to one
blood volume in 24 h (eg, 10 units in a 70-kg
adult).
 DIC: When a patient receives stored blood in
such large volume, the patient's own blood
may be, in effect, “washed out.” In
circumstances uncomplicated by prolonged
hypotension or DIC, dilutional
thrombocytopenia is the most likely
complication.

82.  Platelets in stored whole blood are not
functional. Clotting factors (except factor VIII)
usually remain sufficient.
 Microvascular bleeding (abnormal oozing
and continued bleeding from raw and cut
surfaces) may result.
 Five to 8 (1 unit/10 kg) platelet concentrates
are usually enough to correct such bleeding
in an adult.
 Fresh frozen plasma and cryoprecipitate may
be needed.

83. VII. TRANSMISSION OF INFECTIONS
 These may be:
 Hepatitis B & C
 HIV
 HTLV
 Cytomegalovirus (CMV)
 Epstein-Barr virus
 Human Parvovirus (B19)
 Human Herpes virus
 Syphilis
 Malaria

84. SUMMARY
?

85. THE END