HEMOSTASIS, BLOOD

PRODUCTS, AND BLOOD

TRANSFUSION

RAKAN TELFAH

HEMOSTASIS Is a process to prevent and stop bleeding, meaning to keep blood

within a damaged blood vessel (the opposite of hemostasis is

hemorrhage.)

Red blood cells appear to play an

important role in platelet adhesion

and aggregation, potentially because

of their physical capability to

facilitate platelet transport to the

surface . Therefore, adequate function

of primary hemostasis is dependent on a

sufficiently high hematocrit

membrane-associated

glycoprotein that is not in

contact with the blood under

physiological circumstances

**present at subendothelial sites

.

fibrinolysis

present in

endothelial cells

by various stimuli, including

hypoxia and acidosis, as may

occur during thrombotic occlusion.

By protein C

● So An imbalance between activators and inhibitors of the fibrinolytic

system, resulting in a net antifibrinolytic state, may contribute to the

development of thrombosis

● The efficacy of postoperative pneumatic calf compression may be

based not only on rheological advantages in the venous circulation but

also result from the enhanced release of plasminogen activators from

the vessel wall upon compression (and venous occlusion), thereby

compensating for this fibrinolytic imbalance.

NATURAL ANTICOAGULANT MECHANISMS :

NATURAL ANTICOAGULANT MECHANISMS :

● Activation of the coagulation system is regulated at various points .

● Inhibition of the tissue factor–factor VIIa complex may occur by the action of tissue factor

pathway inhibitor (TFPI), a surface-associated protease inhibitor.

● Further regulation takes place by the protein C system. Activated protein C, assisted by its

essential cofactor (protein S), proteolytically degrades the important cofactors V and VIII.

Activated protein C is formed upon activation of circulating protein C by the endothelial cell-

bound enzyme thrombomodulin in association with thrombin. Hence, thrombin not only

plays a pivotal role in coagulation activation but is also involved in the inhibition of blood

coagulation. Both protein C and protein S are vitamin K-dependent proteins.

● A third inhibitory system is formed by antithrombin III: This serine protease inhibitor forms

complexes with thrombin and factor Xa, thereby losing their coagulant activity.

● >>The inhibitory action of antithrombin III on thrombin and factor Xa is strongly amplified in

the presence of heparin.

A situation in which there is normal functional protein C but an impaired sensitivity of factor

V to protein C is called activated protein C resistance (APC resistance) and is caused by a

point mutation in factor V (factor V Leiden). The prevalence of this mutation is about 3% to

5% in the general population and may account for about 30% of all idiopathic venous

thromboembolism.

LABORATORY MONITORING OF BLEEDING AND COAGULATION:

Peripheral platelet count:

at least should be 30 to 50 *10 ^ 9.

Counts of less than 10,000 \ μL are dangerous and may lead to

spontaneous bleeding as bleeding from the urinary system, GI,

or from any simple trauma

there will be bleeding from the skin. [These are signs of platelets

problem]

Approach:

1) History

2) Physical examination

Investigations:

Pre OP clinics

These are done for etiological Factors in bleeding

Prior to surgery, platelet count should be raised depending on the

site of surgery .

Ex. surgery on gallbladder you can do the surgery even if the platelet

count was 50,000 \ μL

while if going to work on tonsils you must be sure that the platelets

count is high.

Thrombocytosis is diagnosed when count is more than 500,000 \μL

BLEEDING TIME usually shorter than 8 minutes

if prolonged :

low plasma level of vWF /IX /V

use of antiplatelets drugs [Aspirin]

presence of lupus-like antibodies

platelet functional impairment.

Fibrinogenemia.

COAGULATION TESTS:

PT [Prothrombin Time] (extrinsic system) Factor VII (11-13 seconds.)

monitoring of warfarin treatment.

•INR = [Patient PT ÷ Control PT]ISI

Unlike the PT, the results of the INR will be similar on a blood sample

tested in any laboratory using any thromboplastin

reagent/instrument system when calibrated correctly

Coagulation tests must be

performed on plasma rather

than serum, because clotting

factors are removed during

serum preparation along with

the clotted cellular elements.

USES OF THE PT/INR

Clinical uses of the PT include the following:

●Evaluation of unexplained bleeding

●Diagnosing disseminated intravascular coagulation

●Obtaining a baseline value prior to initiating anticoagulation

●Monitoring warfarin therapy

●Assessment of liver synthetic function

PTT [Partial Thromboplastin Time ]

(intrinsic pathway) Factors XII, XI, IX, VIII

(25-35 seconds.)

USES OF THE APTT

Clinical uses of the aPTT include the following :

●Evaluation of unexplained bleeding

●Diagnosing disseminated intravascular coagulation (DIC)

●Monitoring therapy with unfractionated heparin

●Monitoring therapy with parenteral direct thrombin inhibitors

“dabigatran”

Of note, low molecular weight (LMW)

heparins often do not prolong the

aPTT.

While the PT and aPTT provide an overall assessment of clot

formation, they do not provide information about fibrin cross linking

or clot dissolution and will thus be insensitive to abnormalities of

factor XIII function or abnormal fibrinolysis.

READING RESULTS normal PT and PTT, --- vessels or platelets.

PT and PTT are prolonged, --- common pathway

PTT is prolonged and PT is normal, --- intrinsic pathway

Prolonged PT and normal PTT --- factor VII

BLEEDING DISORDERS Vascular defect

platelet defect (thrombocythemia/ thrombocytopenia/

thrombasthenia.)

defect in clotting mechanism (hereditary/ acquired.)

DIC : Disseminated Intravascular Coagulation, or Acquired Hypofibrinogenemia Systemic activation of

coagulation pathways

Excessive Thrombin generation • Diffuse microthrombi • Consumption and depletion of Platelets and

coagulation factors • Classic picture of diffuse bleeding

DIC Diagnosis: • The presence of inciting underlying pathology • Low Platelets • Prolonged PT/PTT •

Low Fibrinogen levels • high FDPs.

DIC Treatment: • Relieving

inciting factor • Adequate

perfusion • FFP •

Cryoprecipitate,Platelets and/or

Factor supplements.

Measurement of fibrinogen is commonly performed but has

shown to be of no value for the diagnosis of DIC, especially

because the acute-phase reactant properties of

fibrinogen in many clinical situations may completely

obscure ongoing fibrinogen consumption.

most common cause strong predictor of death +

COAGULOPATHY OF LIVER DISEASE

•Prolonged PT • Thromboses )protein C and S deficiency)………

disturbance in the balance between procoagulant and anticoagulant

pathways…. both increased bleeding risk and increased thrombotic

risk

thrombocytopenia and impaired humoral coagulation function

manifested as prolongation PT/INR

• . The etiology of thrombocytopenia in patients with liver disease

•1 ) hypersplenism • 2) reduced production of thrombopoietin

•3 ) immune-mediated destruction of platelet

● Platelet transfusions are the mainstay of therapy; however, the

effect typically lasts only several hours….risk of antibodies

● administration of interleukin-11 (IL-11), a cytokine that stimulates

proliferation of hematopoietic stem cells and megakaryocyte

progenitors.(cancer patient and cirrhotic patient)

● splenectomy or splenic embolization to reduce

hypersplenism.(less used)

COAGULOPATHY OF TRAUMA due to

•1 ) acidosis >> decrease o2 supplement

•2 ) hypothermia ,

•3 ) dilution of coagulation factors.

•Local Hemostasis :

•Digital pressure • Tourniquet

•Packing

•Biological agents that help platelets adhesion

PRO HEMOSTATIC AGENT in patients with :

coagulation defects

severe (postoperative) bleeding

who undergo procedures known to be associated with major blood

loss •

PLATELETS, PLASMA, AND COAGULATION FACTOR .

PLATELETS usually contain a mixture of the platelet from six donors (6 units). After

platelet transfusion, the platelet count should rise by at least 5*10^9 /l per

unit of platelets transfused.

Indications: Amegakaryocytic thrombocytopenia, Drug or radiation induced

hypoplasia, functional platelet abnormalities, viral diseases associated with

thrombocytopenia e.g. Dengue, Disseminated intravascular coagulation.

Dengue

1. platelet consumption during ongoing coagulopathy process

2. activation of the complement system

3. increased peripheral sequestration

FRESH FROZEN PLASMA plasma separated from whole blood donation within 6 hours and then rapidly frozen to –

25°C or colder, shelf life up to 1 year

contains factor VIII, factor IX, vWF and other clotting factors. Fibrinogen

Dosage: Initial dose of 15 ml/kg. Labile coagulation factors rapidly degrade; use within 6

hours of thawing.

Indications :-

CRYOPRECIPITATE Storage: At –25°C or colder for up to 1 year

Must be infused within 6 hours of thawing

Each unit of Cryo raises Factor VIII by 2%, to achieve plasma factor

VIII rise of 20%, 10 units/kg have to be infused .

Indications: in the treatment of inherited deficiencies of von

Willebrand Factor )von Willebrand’s disease( / Factor VIII

(haemophilia A) / Factor XIII As a source of fibrinogen in acquired

coagulopathies: e.g. disseminated intravascular coagulation (DIC)

SPECIFIC FACTORS “PURIFIED CONCENTRATES”

factor VIII in )hemophilia A and von Willebrand’s disease)

factor IX in (hemophilia B or Christmas disease)

In general, activity levels should be restored to 30% to 40% for mild

hemorrhage, 50% for severe bleeding, and 80% to 100% for life-

threatening bleeding .

INDICATIONS OF BLOOD TRANSFUSION :

In general , blood loss or low hemoglobin .

•1 ) Improvement in Oxygen-Carrying Capacity .

•2 ) Treatment of Anemia

•3 ) Volume Replacement

BANKED WHOLE BLOOD

● shelf life of red blood cells is now 42 days.

● The changes in the red blood cells that occur during storage

include reduction of intracellular ADP and 2,3-diphosphoglycerate

(2,3DPG), which alters the oxygen dissociation curve of

hemoglobin, resulting in a decrease in oxygen transport

● Stored RBCs progressively becomes acidic with elevated levels

of lactate, potassium, and ammonia.

● Whole blood is only indicated for the treatment of acute

hemorrhage.

RED BLOOD CELLS AND FROZEN RED BLOOD CELLS

● Red blood cells are the product of choice for most clinical situations

requiring resuscitation.

● Concentrated suspensions of red blood cells can be prepared by

removing most of the supernatant plasma after centrifugation.

● not currently available for use in emergencies, as the thawing and

preparation time is measured in hours.

● The red blood cell viability is improved, and the ATP and 2,3-DPG

concentrations are maintained.

● The preparation reduces but does not eliminate reactions caused by

plasma components .

HAZARDS OF TRANSFUSION

•10 % of all transfusions

•Less than 0.5% are serious

•Non hemolytic reactions

•1 %

•Rise in Temp. more than 1C ……………antibodies directed against donor leukocytes and

HLA antigens

•Bacterial contamination

•Allergic reactions

•Respiratory(TACO).. Transfusion-associated circulatory overload • TRALI

•Hemolytic reactions

IMMEDIATE HEMOLYTIC

TRANSFUSION REACTION: ABO incompatibility

Fatal in 6% of cases

Hemoglobinemia and Hemoglobinuria (usually acidic )

Deaths occur from DIC and acute renal failure

Clinical presentation in Immediate hemolytic reaction: [in

order]

Burning sensation at the transfusion site followed by Anxiety, Chest

pain (tightness), Back pain, headache, Dyspnea, Rigors [Chills],

Vomiting, Diarrhea, Restlessness, Tachycardia, Hypotension, Shock.

Treatment:

1 . Stop transfusion immediately.

2 . Give Hydrocortisone 100-200 mg I.V.

3 . Anti-histamine (chlorpheneramine 10mg) I.V.

4 . Intravenous fluid to maintain the blood volume and urinary flow.

5 . In case of intravenous coagulation give Heparin.

DELAYED HEMOLYTIC TRANSFUSION REACTION:

Occurs 1-3 weeks after transfusion.

Clinical presentation in Delayed hemolytic reaction:

Patient comes with Urticaria [due to Plasma proteins] esp. in people

with IgA deficiency, jaundice, fever,

anemia, arthralgia and myalgia [muscle pain.]

Treatment: None in required just observation.

MASSIVE BLOOD TRANSFUSION ● It is most often defined as the need to transfuse the patient’s

total estimated blood volume in less than 24 h, or one-half the

patient’s total estimated blood volume in 1 h. For most adult

patients, the total estimated blood volume is the equivalent of 10

to 20 units. The approach to massive transfusion (and to lesser

degrees of transfusion) elucidates that the outcomes have

improved with concurrent transfusion of (packed red cells, FFP,

and platelets) to avoid dilutional coagulopathy ……..)1:1:1)

THANK YOU