RBC Disorders

Question 1

In primary hemostasis, what are the 2 products that activate platelets & what 2 products inhibit platelets?

Answer 1

Platelet activators: 1) Thromboxane A2, 2) ADP

Platelet inhibitors: 1) NO, 2) PG

Question 2

What is the function of platelet activators?

Answer 2

They help to activate the platelets so they are 1) more sticky, 2) release more vWF, serotonin (which attracts more plt) Ca2+, ADP, TXA2

Question 3

What is the compound that links all of the platelets together?

Answer 3

Fibrinogen

Question 4

What are the various steps in primary hemostasis?

Answer 4

Adhesion of vWF & plt

Activation of plt

Aggregation of plt

Question 5

What is secondary hemostasis? What is the goal of secondary hemostasis?

Answer 5

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

Question 6

What does factor XIII do?

Answer 6

Cross links the fibrin mesh

Question 7

What are the 3 roles of thrombin (clotting factor II)?

Answer 7

1) activates Factor V, VIII, XI, XIII
2) activates platelets
3) cleaves fibrinogen-fibrin

Question 8

Which clotting factor will degrade in the blood unless bound to vWF?

Answer 8

Factor VIII

Question 9

What releases vWF?

Answer 9

Activated platelets AND endothelial cells

Question 10

What is fibrinolysis?

Answer 10

Degradation of fibrin mesh

Plasminogen converted into plasmin via tPA

Plasmin cuts fibrin mesh

Endothelial cells secrete tPA when exposed to thrombin & Factor X

Question 11

What is d-dimer?

Answer 11

Platelets are attached to a D subunit, when the clot is broken down - D subunit breaks apart from the platelet

Question 12

What clotting factors are dependent on Vitamin K?

Answer 12

X, IX, VII, II (1972)

Question 13

Why can’t those clotting facts become activated without Vitamin K?

What medication affects this pathway?

Answer 13

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

Question 14

What kind of bleeding do you get with disorders of primary hemostasis?

Answer 14

Mucocutaneous bleeding - epistaxis, gingival bleeding, menorrhagia, petechia, GI bleeding

Question 15

What kind of bleeding do you get with secondary hemostasis?

Answer 15

Get more hemarthroses & hematomas

Question 16

3 primary ways in which anemia can occur?

Answer 16

Blood loss
Increased destruction
Decreased production

Question 17

Indications for RBC transfusion

Answer 17

• 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

Question 18

Risks & complications with blood transfusions?

Answer 18

• 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

Question 19

What is the differential for microcytic anemia?

Answer 19

IRON LAST

• iron deficiency anemia
• Lead poisoning
• Anemia of chronic disease?
• Sideroblastic anemia
• Thalassemia

Question 20

What are signs of iron deficiency?

What are symptoms of iron deficiency anemia?

Answer 20

Pallor
Brittle hair
Glossitis
Cheilosis ~ corners of mouth become inflamed
Koilonychia ~ spoon nails ~ become concave

Symptoms

• Pica
• Fatigue
• SOB
• Palpitations
• Pallor
• Weakness
• Dizziness

Question 21

What would you see on a peripheral smear for sickle cell anemia?

Answer 21

• Sickled cells
• Howell Jolly bodies ~ residual RBC nuclei remnants ~ usually removed by spleen but in SCD have asplenia
• Target cells

Question 22

How does sickling of a RBC occur?

What brings on sickling?

What happens to RBC with repeated sickling?

Answer 22

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

Question 23

What is involved in a sickle cell crisis?

Answer 23

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

Question 24

What is the differential for normocytic anemia with a low reticulocyte count?

Answer 24

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

Question 25

What is myelofibrosis, how does it occur & what are clinical features? what would you find on BM aspiration & biopsy?

Answer 25

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,

Question 26

What is the differential for normocytic anemia with a high reticulocyte count?

Answer 26

``` 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

Question 27

How does maternal sensitization occur re: hemolytic disease of a newborn with ABO & Rh blood groups?

Answer 27

- through delivery - through spontaneous/induce abortion - antenatal hemorrhage

Question 28

When is Rhogam given

Answer 28

Given to a Rh- mom at 28 weeks & second dose is within 72 hr of birth

Question 29

What are the complications associated with hemolytic disease of the newborn?

Answer 29

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

Question 30

What is the difference between a direct & indirect coomb’s test?

Answer 30

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

Question 31

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?

Answer 31

Indirect coomb’s test = positive bc antibodies to baby’s RBCs Direct coomb’s test

Question 32

What is TTP? What is the clinical presentation? Smear show?

Answer 32

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

Question 33

When is a type & screen used vs a cross & match?

Answer 33

Type & screen —>used if you might need to give a transfusion Cross & match —> used just before the transfusion (last step before transfusion)

Question 34

What is heparin induced thrombocytopenia?

Answer 34

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

Question 35

What are the clinical features of heparin induced thrombocytopenia?

Answer 35

Venous: DVT, PE, cerebral sinus thrombosis Arterial: MI, CVA, organ ischemia Heparin induced skin necrosis

Question 36

When should you suspect heparin induced thrombocytopenia? How do we treat it?

Answer 36

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

Question 37

What is hemolytic uremic syndrome?

Answer 37

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

Question 38

What is the differential for polycythemia?

Answer 38

Primary —> polycythemia rubra Vera Secondary —> - altitude - iatrogenic: anabolic steroids, testosterone use, EPO administration - relative: third space loss, plasma volume depletion - EPO secreting tumour

Question 39

What is polycythemia rubra Vera?

Answer 39

Genetic disorder where you have mutation in hematopoietic stem cells —> continuously dividing even in absence of EPO Over time te stem cells die = myelofibrosis

Question 40

What complications can occur with polycythemia rubra Vera?

Answer 40

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