hemostasis, blood products, and blood transfusion
TRANSCRIPT
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