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