RBC Disorders Flashcards
In primary hemostasis, what are the 2 products that activate platelets & what 2 products inhibit platelets?
Platelet activators: 1) Thromboxane A2, 2) ADP
Platelet inhibitors: 1) NO, 2) PG
What is the function of platelet activators?
They help to activate the platelets so they are 1) more sticky, 2) release more vWF, serotonin (which attracts more plt) Ca2+, ADP, TXA2
What is the compound that links all of the platelets together?
Fibrinogen
What are the various steps in primary hemostasis?
Adhesion of vWF & plt
Activation of plt
Aggregation of plt
What is secondary hemostasis? What is the goal of secondary hemostasis?
Clotting cascade
Involves intrinsic & extrinsic pathway & common pathway
Intrinsic requires Factor XII to bump into the platelet plug
Extrinsic activated when endothelium is damaged & releases tissue factor (III)
Goal is to produce fibrin mesh
What does factor XIII do?
Cross links the fibrin mesh
What are the 3 roles of thrombin (clotting factor II)?
1) activates Factor V, VIII, XI, XIII
2) activates platelets
3) cleaves fibrinogen-fibrin
Which clotting factor will degrade in the blood unless bound to vWF?
Factor VIII
What releases vWF?
Activated platelets AND endothelial cells
What is fibrinolysis?
Degradation of fibrin mesh
Plasminogen converted into plasmin via tPA
Plasmin cuts fibrin mesh
Endothelial cells secrete tPA when exposed to thrombin & Factor X
What is d-dimer?
Platelets are attached to a D subunit, when the clot is broken down - D subunit breaks apart from the platelet
What clotting factors are dependent on Vitamin K?
X, IX, VII, II (1972)
Why can’t those clotting facts become activated without Vitamin K?
What medication affects this pathway?
Vitamin K is cofactor needed for a series of conversion that leads to the activation of those clotting factors
Warfarin ~ affects epoxide reductase = responsible for converting Vitamin K into its co-factor from
What kind of bleeding do you get with disorders of primary hemostasis?
Mucocutaneous bleeding - epistaxis, gingival bleeding, menorrhagia, petechia, GI bleeding
What kind of bleeding do you get with secondary hemostasis?
Get more hemarthroses & hematomas
3 primary ways in which anemia can occur?
Blood loss
Increased destruction
Decreased production
Indications for RBC transfusion
- symptomatic anemia
- sickle cell crisis
- acute blood loss >30% volume
- Transfuse when Hb <70 for all patients except those who:
— hemodynamically unstable ~ transfuse before
— Stable CV or ACS ~ transfuse before
— Acute orthopaedic or cardiac surgery ~ transfuse before
— severe treatment related to thrombocytopenia
Risks & complications with blood transfusions?
- infection
- allergic or immune transfusion reaction (acute transfusion reaction OR delayed)
- volume overload
- hyperkalemia ~ bc K+ release from RBCs during storage bc some get damaged
- iron overload
What is the differential for microcytic anemia?
IRON LAST
- iron deficiency anemia
- Lead poisoning
- Anemia of chronic disease?
- Sideroblastic anemia
- Thalassemia
What are signs of iron deficiency?
What are symptoms of iron deficiency anemia?
Pallor
Brittle hair
Glossitis
Cheilosis ~ corners of mouth become inflamed
Koilonychia ~ spoon nails ~ become concave
Symptoms
- Pica
- Fatigue
- SOB
- Palpitations
- Pallor
- Weakness
- Dizziness
What would you see on a peripheral smear for sickle cell anemia?
- Sickled cells
- Howell Jolly bodies ~ residual RBC nuclei remnants ~ usually removed by spleen but in SCD have asplenia
- Target cells
How does sickling of a RBC occur?
What brings on sickling?
What happens to RBC with repeated sickling?
When oxygenated it can carry it appropriately, but when deoxygenated, the Hb proteins stick together in the RBC & form that crescent shape
- Acidosis, low flow vessels (Hb has lots of time to give away its oxygen), fevers
- damages the membrane & promotes destruction of the RBC —> leads to anemia, increased Hb recycling & build up of UCB - signs of jaundice
What is involved in a sickle cell crisis?
1) aplastic crisis
- Parvovirus B19
- virus infects RBC in BM ~ impairs cell division for a few days
- in N pts ~ drop in minor drop in Hb, in SC pt ~ severe drop in Hb
- self limiting
2) Splenic sequestration
- occurs in childhood
- blood pools in spleen & acute drop in Hb
- doesn’t really occur in adults bc of splenic infarction
3) vaso-occlusive crisis
- sickled RBC occlude vessels —> ischemia-reperfusion injury (heart ~ MI, spleen ~ splenic infarct, brain ~ CVA)
4) acute chest syndrome
- pulmonary micro vascular conclusions ~ common cause of death
What is the differential for normocytic anemia with a low reticulocyte count?
PANCYTOPENIA L-leukaemia A-aplastic anemia M-myelofibrosis B- BM invasion/suppression
NON-PANCYTOPENIA
L- liver failure
A - anemia of chronic disease
R - renal failure
What is myelofibrosis, how does it occur & what are clinical features? what would you find on BM aspiration & biopsy?
BM fibrosis leading to BM failure
Can be primary (genetic. ~ leads to fibroblasts laying down fibrin - fills BM & replaces hematopoietic stem cells) or secondary
CF: Sx ~ anemia: fatigue, palpitations, dizziness, pallor, cold extremities + bone pain + hepatosplenomegaly
BM aspiration - “dry tap”
BM biopsy - Fibrosis, thickening of trabeculae,
What is the differential for normocytic anemia with a high reticulocyte count?
HEMOLYTIC - Hereditary — G- G6PD — T - thalassemia — S - spherocytosis
- Acquired
— D - disseminated intravascular coagulation
— O - oxidative/drug related
— I - infection (malaria)
— T - TTP: thrombotic thrombocytopenic purpura
— H - HUS: hemolytic uremic syndrome
— H - HELLP: hemolytic anemia, elevated liver enzymes, low platelets
— H - Hemolytic disease of the newborn
Post-hemorrhagic causes
- GU, GI, other
How does maternal sensitization occur re: hemolytic disease of a newborn with ABO & Rh blood groups?
- through delivery
- through spontaneous/induce abortion
- antenatal hemorrhage
When is Rhogam given
Given to a Rh- mom at 28 weeks & second dose is within 72 hr of birth
What are the complications associated with hemolytic disease of the newborn?
Kernicterus
Hyperbilirubinemia
Hydros fetalis —> edema over whole body (subq tissue, pleural/pericardial effusions, ascites ~ in all body cavities) bc related to severe anemia-induced hypoxemia
What is the difference between a direct & indirect coomb’s test?
Direct Coomb’s Test
- Diagnose the cause of hemolytic anemia
- Detects the presence of antibodies attached to RBCs
- Procedure: Pts RBCs get washed (free floating antibodies are removed), add IgG coomb’s agent & if the patient does have hemolytic anemia ~ IgG coomb’s agent will attach to antibodies already on RBCs —> POSITIVE TEST
INDIRECT COOMB’S TEST
- Only used for “pre-transfusion” testing
- Looking for antibodies in the recipient’s blood to donor’s RBCs
- Procedure:
— Recipient’s blood: separated the serum (has all antibodies) from the RBCs THEN mix the Donor’s RBCs with the Recipient’s serum PLUS Coomb’ reagent, if not a match = agglutination of RBCs & antibodies = POSITIVE TEST
What would you see on antenatal testing for a patient with hemolytic disease of the newborn regarding coomb’s tests?
At birth is this different?
Indirect coomb’s test = positive bc antibodies to baby’s RBCs
Direct coomb’s test
What is TTP?
What is the clinical presentation?
Smear show?
Thrombotic thrombocytopenic purpura —> genetic disorder where have reduced activity of ADAMTS13 -> increased amount vWF on endothelial surface of b.v —> plt to attach-aggregate-active —> small clots forming
Does 2 things: 1) use up all your plt - low plt, 2) clots forming all over body ~ contributing to a level of ischemic, 3) clots damage RBCs pass by & so you get hemolytic anemia, 4) bc using up all your plt you get mucocutaneous bleeding
CP: - classic pentad: - Microangiopathic hemolytic anemia - thrombocytopenia - Renal insufficiency ~ AKI - fever - neurological dysfunction (HA, confusion, seizures, coma) \++ mucocutaneous bleeding: epistasix, purpura/petechiae, gingival bleeding \++dark urine
Smear ~ schistocytes
When is a type & screen used vs a cross & match?
Type & screen —>used if you might need to give a transfusion
Cross & match —> used just before the transfusion (last step before transfusion)
What is heparin induced thrombocytopenia?
Heparin binds to plt & in some people is immunogenic = tagged by IgG for destruction == low plts
PLUS heparin binding to plt activates platelet = clot formation = uses up all plt
Increased risk of bleeding ++ clot formation causing thrombotic events
What are the clinical features of heparin induced thrombocytopenia?
Venous: DVT, PE, cerebral sinus thrombosis
Arterial: MI, CVA, organ ischemia
Heparin induced skin necrosis
When should you suspect heparin induced thrombocytopenia?
How do we treat it?
If pt recently started heparin OR plt count has dropped within 1-2 weeks or 1 day (with previous heparin use)
D/C any form of heparin (UFH, LMWH), start on fondaparinux
2-3 mon if no thrombotic event
3-6 mon if thrombotic event
What is hemolytic uremic syndrome?
Caused by shiga toxin (e coli) —> absorbed through intestines - damages cells here ~ hematochezia
Filtered by kidneys ~ damages tiny b.v here - AKI PLUS tiny clots form here - uses up plt (low plts) & MAHA bc of the clots causing damage to the RBCs
What is the differential for polycythemia?
Primary —> polycythemia rubra Vera
Secondary —>
- altitude
- iatrogenic: anabolic steroids, testosterone use, EPO administration
- relative: third space loss, plasma volume depletion
- EPO secreting tumour
What is polycythemia rubra Vera?
Genetic disorder where you have mutation in hematopoietic stem cells —> continuously dividing even in absence of EPO
Over time te stem cells die = myelofibrosis
What complications can occur with polycythemia rubra Vera?
Increased cell volume leads to abnormal flow of blood ~ dysfunction of plt
Clotting + Bleeding disorders: DVT, PE, MI, Budd-Chiari syndrome, can even progress to AML
