Hematology Physiology Flashcards
♣ Based on carbohydrate antigens (A and B) present on RBC membrane either as glycoprotein or glycosphingolipids
♣ All individuals produce antibodies to the AB carbohydrate antigen that they lack
♣ Two genes, one on each of two paired chromosomes, determine the O-A-B blood type
Blood Groups
Why are agglutinins produced in people who do not have the respective agglutinogens in their red blood cells?
Small amounts of these agglutinogens enter through food and bacteria which initiate the production of agglutinins.
Universal Donor
Blood Type O
Universal Recipient
Blood Type AB
♣ Blood group with 6 antigens: C, D, E, c, d, e
♣ Agglutinins are produced after massive exposure to the Rh agglutinogens
♣ Most widely prevalent antigen is D
Rh Blood Group
If you have the D antigen
Rh+
If you do not have D antigen or you have the rest of the antigens
Rh-
Identifying blood type (ABO with Anti-A and Anti-B sera and Rh with anti-D serum)
♣ “Forward” Identify antigen by antisera
♣ “Reverse” Identify isoagglutinin in serum
Pretesting of Blood
Antigen-antibody complexes causes agglutination ->
Clumps of RBCs pass thru small blood vessels ->
Physical distortion, phagocytic attack in a few days ->
Delayed hemolysis
Massive amounts of antibodies meet antigenic donor RBCs -> Activate complement and rupture of membranes ->
Immediate hemolysis
- Increases oxygen-carrying capacity and volume expansion
- Ideal for cases of acute hemorrhage of more than 25% of blood volume
Whole Blood
- Increase oxygen-carrying capacity
- Should only be given to those with anemia and symptoms
o Dizziness
o Increased heart rate
o Difficulty of breathing
Packed Red Blood Cells
- Reduces risk of mucosal bleeding
Platelet concentrates
Thresholds for transfusion of Platelet concentrates
o Patient w/o fever or infection 5,000/uL
o Patient w/ fever of infection 10,000/uL
o Undergoing invasive procedue 50,000/uL
- Contains stable coagulation factors and plasma proteins (fibrinogen, antithrombin, albumin, proteins C and S)
- Indications
o Correction of coagulopathies, including the rapid reversal of warfarin
o Supplying deficient plasma proteins
o Treatment of thrombotic thrombocytopenic purpura
Fresh Frozen Plasma
− Supplies fibrinogen, factor VIII, and von Willebrand factor (vWF)
− Each units contains 80 units Factor VIII
− Lesser volume than FFP
Cryoprecipitate
− Contains Factor IX (hemophilia B)
Cryosupernate
Adverse Reactions to Transfusion
♣ Immunologic
♣ Non-immunologic
♣ Infections
prevention of blood loss
Hemostasis
Stages of Hemostasis
- Reflex Vasoconstriction
- Primary Hemostasis
- Secondary Hemostasis
- Clot Retraction or Clot Dissolution
♣ Results in immediate reduction in bleeding
♣ Mechanisms:
a. Local myogenic spasm– strongest contributor
b. Local autocoid factors from platelets and injured tissues e.g. Thromboxane A2, Endothelin (for ruptured blood vessel)
c. Nervous reflexes – from pain and other sensory impulses
Reflex Vasoconstriction
♣ Formation of the primary thrombi or platelet plug
♣ Responsible for hemostasis of small vessels
♣ Involves platelets (key player), the blood vessel wall and von Willebrand factor (vWF)
Primary Hemostasis
♣ Also called thrombocytes
♣ 1-4 μm, no nuclei and do not reproduce
♣ Originate from megakaryocytes
♣ Normal count: 150,000 to 450,000 per microliter
♣ Half-life: 8 to 12 days in the circulation
♣ Eventually cleared by macrophages in the blood and in the spleen
Platelet
Stages in the Formation of the Platelet Plug
- Platelet adhesion
- Platelet activation
- Platelet aggregation
♣ Caused by low platelet count or abnormal platelet function
♣ Present as small hemorrhages in the skin and mucous membranes (small vessels)
Abnormality in Platelets
♣ Initiates the coagulation cascade
♣ Can be explosive
♣ Limited by quantities of traumatized tissue, Factors X, VII and V
♣ Clotting can occur in 15 seconds
Extrinsic Pathway
- Amplifies the cascade
- Slower, clotting in 1 to 6 minutes
Intrinsic Pathway
In which part of the coagulation cascade does the extrinsic and intrinsic pathways converge?
Factor Xa-mediated generation of thrombin from prothrombin
♣ Fibrin clot is invaded by fibroblasts which subsequently form connective tissue around the clot.
♣ Calcium from platelets stores also contribute to this
♣ As clot retracts, edges of the injured vessel are pulled together further reducing blood loss
Clot Retraction
♣ Mediated by anticoagulant and thrombolytic mechanisms
Clot Dissolution
What are other factors/molecules involved in the coagulation cascade?
Calcium, Vitamin K Anticoagulant Mechanisms
involved in all steps in the cascade except the first 2 steps in the intrinsic pathway
Calcium
required to produce prothrombin and other clotting factors in the liver
Vitamin K
♣ Smooth endothelium
♣ Glycocalyx layer that repels platelets and clotting factors
♣ Thrombomodulin
- Secreted by the endothelium
- Binds thrombin thereby reducing free thrombin
- Activates Protein C which inactivates Factor V and VIII
Endothelium
♣ 85 to 90% of the thrombin becomes adsorbed into the fibrin fibers
♣ Antithrombin III inactivates thrombin
♣ Heparin increases activity of antithrombin III hundredfold to thousandfold
Low concentrations in the body but is an extremely useful drug
Intravascular anticoagulants
factor VIII deficiency
Hemophilia A
factor IX deficiency
Hemophilia B
is also known as immediate or anaphylactic hypersensitivity. The reaction may cause a range of symptoms from minor inconvenience to death. The reaction usually takes 15 - 30 minutes from the time of exposure to the antigen, although sometimes it may have a delayed onset (10 - 12 hours).
Type I hypersensitivity
Immediate hypersensitivity is mediated by
IgE
The primary cellular component in this hypersensitivity is the
Mast Cell or Basophil
also known as cytotoxic hypersensitivity and may affect a variety of organs and tissues. The antigens are normally endogenous, although exogenous chemicals (haptens) which can attach to cell membranes can also lead to type II hypersensitivity. Drug-induced hemolytic anemia, granulocytopenia and thrombocytopenia are such examples.
Type II hypersensitivity
Type II hypersensitivity is primarily mediated by antibodies of the
IgM or IgG classes and complement
is also known as immune complex hypersensitivity. The reaction may be general or may involve individual organs including skin (e.g., systemic lupus erythematosus, Arthus reaction) or other organs. This reaction may be the pathogenic mechanism of diseases caused by many microorganisms.
Type III hypersensitivity
They are mostly of the IgG class, although IgM may also be involved.
Type III hypersensitivity
is also known as cell mediated or delayed type hypersensitivity. The classical example of this hypersensitivity is tuberculin (Montoux) reaction (figure 5) which peaks 48 hours after the injection of antigen (PPD or old tuberculin).
Type IV hypersensitivity
Blood loss anemia
Microcytic, hypochromic anemia
Anemia where RBCs grow too large with odd shape
Megaloblastic Anemia
Pathological condition caused by a genetic aberration in the hemocytoblastic cells that produce the red blood cells
Polycythemia Vera
