HEMOSTASIS

&

BLOOD TRANSFUSIONBy

Dr. Abdul Qadeer MemonMBBS; FCPS; FICS

Assistant Professor in General Surgery

King Faisal University College of Medicine

Kingdom of Saudi Arabia

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

1. DEFINITION OF HEMOSTATSIS

Heme = Blood + Stasis = To halt

(Stop)

It is the process of forming clots in the wallof damaged blood vessels & preventingblood loss while maintaining blood in afluid state within the vascular system.

Spontaneous arrest of bleeding byphysiological process.

MAINTAINS BLOOD FLOW

PREVENTS BLOOD

LOSS

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

STAGES OF HEMOSTASIS

STAGES OF HEMOSTASIS

A) VASCULAR PHASE OF HEMOSTATSIS

VASCULAR PHASE OF HEMOSTATSIS

B) PLATELET PHASE

PLATELET PHASE (PLATELET PLUG)

C) COAGULATION PHASE (BLOOD CLOT)

D) CLOT RETRACTION

Release of fibrin stabilizing factor

Contractile protein of platelets

Activated and accelerated by thrombin and

Ca+2 ions.

E) FIBRINOLYSIS

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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

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

PETECHIAE, PURPURA HEMATOMA, JOINT BL.

PLATELET COAGULATION

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

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

OTHER TESTS FOR HEMOSTASIS

Thrombin time

INR = International Normalized Ratio

PLATELET COUNT

NORMAL 150,000 - 400,000

Cells/mm3

< 100,000 Thrombocytopenia

50,000 - 100,000 Mild Thrombocytopenia

< 50,000 Severe Thrombocytopenia

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

CLOTTING (COAGULATION) TIME (CT)

The time required for blood to clot in a glass

tube

Normal value

5-15 Min

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

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

THROMBIN TIME (TT)

Time for Thrombin To Convert Fibrinogen into

Fibrin

A Measure of Fibrinolytic Pathway

Normal value

9-13 sec

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

SIGNIFICANCE OF INR

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

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4. MAJOR DISORDERS OF HEMOSTASIS

INHERITED

Vascular

Platelet

Coagulation

Fibrinolytic

ACQUIRED

Vascular

Platelet

Coagulation

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.

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.).

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).

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).

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.

COAGULOPATHIES

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.

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5. BLOOD COMPONENTS

BLOOD COMPONENTS (%)

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

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

B. BLOOD PRODUCTS RELATED TO PLATELETS

These include:

i. Platelet rich plasma

ii. Platelet concentrate

iii. Frozen platelets

C. BLOOD PRODUCTS RELATED TO LEUCOCYTES

These include:

i. Granulocyte rich plasma

ii. Lymphocyte rich plasma

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

E. BLOOD PRODUCTS RELATED TO SERUM

These include:

i. Normal pool serum

ii. Freeze dried serum

iii. Serum immune globulin

iv. Normal serum albumin

F. BLOOD PRODUCTS RELATED TO ARTIFICIAL

BLOOD

Theses include red cell substitutes

G. BLOOD PRODUCTS RELATED TO PLASMA

SUBSTITUTE

This includes 6% Dextran solution

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6. INDICATIONS FOR COMPONENT THERAPY

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

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

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

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

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

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

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

Disadvantages:

Platelets transfusion is not indicated in;

a. ITP

b. Drug induced thrombocytopenia

c. Extrinsic platelet dysfunction e.g. vWD and

uremia

FRESH FROZEN PLASMA (FFP)

Can be used in patients with:

Coagulation factors deficiency

Hypovolemia

Shock, acute hemorrhage, plasma loss e.g.

in burns

CRYOPRECIPITATE/FACTOR VIII CONCENTRATE

Used in hemophilia or vWD

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

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

SERUM ALBUMIN

Prepared by the fractionation of pooled

plasma

Available in 5% and 25%

Uses:

a. To maintain blood volume

b. Hypoprteinemia

ARTIFICIAL BLOOD RELATED TO RED

BLOOD CELL SUBSTITUTES

Perflouro carbon

Stroma free hemoglobin

6% DEXTRAN SOLUTION

Related to plasma substitutes e.g.

i. Intradex

ii. Dextraven

iii. SAG-M

iv. Ad-sol

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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

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.

I. TRANSUSION REACTIONS

WHAT TO DO? Prompt reporting to blood bank

Stop transfusion immediately

Continue I/V fluids e.g. N. saline

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

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.

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.

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.

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.

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, dilutionalthrombocytopenia is the most likely complication.

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.

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

SUMMARY

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THE END