Hematology Flashcards
What are the most common complications of lead poisoning in infants and children?
- Neurotoxicity can lead to long standing behavioral problems and developmental delay or regression.
- Hemolytic anemia
How does anemia result from lead poisoning?
- There is inhibition of ferrochelatase and aminolevulinic acid dehydratase in heme synthesis pathway.
- Protoporphyrin IX cannot combine with Fe2+ to form heme due to ferrochetolase inhibition.
- Instead it incorporates zinc ion and leads to elevated zinc protoporphyrin levels.
- ALA levels are also increased and accumulated.
Who is at risk for lead poisoning?
- Impoverished children residing in deteriorating urban houses built before 1978.
- Young children are particularly susceptible via inhalation and ingestion of lead based paint dust or chips from crawling and mouthing behaviors.
What is the cause of paroxysmal nocturnal hemoglobinuria (PNH)?
- An acquired mutation of the phosphatidylinositol glycan class A (PIGA) gene within a clonal population of multipotent hematopoietic stem cells.
- Gene is involved in the synthesis of glycosylphosphatidylinositol (GPI) anchor, necessary for the attachment of CD55 and CD59.
What does CD55 and CD59 do?
Help inactivate complement and prevent the membrane attack complex from forming on normal cells.
What is von Willebrand Disease? How is it inherited? What does it cause and lead to? Which factor is decreased? What happens to pTT?
- Most common inherited bleeding disorder
- Autosomal dominant with variable penetrance
- Causes coagulation pathway abnormalities due to decreased factor VIII activity (prolonged pTT)
- Leads to impaired platelet function (prolonged bleeding time)
How does Acute Hemolytic Transfusion Reaction present?
- Presents with fever, chills, hypotension, dyspnea, chest and back pain and hemoglobinuria (red/brown urine).
- May develop DIC and ARF
- Occurs within minutes to hours after blood transfusion
- Due to ABO incompatibility between donor and recipient
What is the mechanism behind an Acute Hemolytic Transfusion Reaction?
- Antibody-mediated (type II) hypersensitivity reaction
- Anti-ABO antibodies, mainly IgM in the recipient bind to corresponding antigens and transfused donor erythrocytes leading to complement activation
- Anaphylatoxins (C3a and C5a) cause vasodilation and symptoms of shock
- Formation of MAC (C5b-C9) leads to compliment-mediated cell lysis
What is protamine used for and what is its action?
- Used for reversal of heparin
- Binds and chemically inactivates heparin
What is fresh frozen plasma used for and what is its action?
- Rapidly reverses warfarin induced anticoagulation
- Used for life threatening bleeding
- Contains all the coagulation factors
What is Vitamin K?
What is it used for?
What is its action and on which factors?
- Procoagulant
- Can reverse warfarin, however it takes time to for the clotting factors to resynthesize
- Vitamin K epoxide reductase is inhibited by warfarin
- Causes g-carboxylation of glutamic acid residues of clotting factors II, VII, IX and X, protein C and S
- Neonates lack enteric bacteria which produce vitamin K
What is Warfarin?
What is it used for?
What is its action and on which factors?
What does it cause?
- Most common long term anticoagulation agent
- Used in venous thrombosis and pulmonary thromboembolism
- Inhibits vitamin K dependent g-carboxylation of the glutamic acid residues of clotting factors II, VII, IX and X
- Causes production of dysfunctional coagulation proteins
Disseminated Intravascular Coagulation in Pregnancy
What causes it?
How does it present?
- Due to release of tissue factor (thromboplastin) from an injured placenta (placental abruption) into the maternal circulation
- Presents with bleeding from incision sites, intravenous line sites and mucosal surfaces due to rapid consumption of clotting factors and platelets
- May present with vaginal bleeding, uterine tenderness, retroplacental hematoma and fetal demise
- Placental abruption may result from severe hypertension
When is Clopidogrel used?
- When a patient has asthma allergy
- It irreversibly blocks P2Y12 component of ADP receptors on the platelet surface and prevents platelet aggregation
- As effective as aspirin for cardiovascular events in patients with coronary artery disease
- Ex patient with stable angina with allergy to aspirin
What is Cilostazol used for?
A phosphodiesterase inhibitor used in patients with peripheral vascular disease
What is the cause of hereditary spherocytosis?
- Defective binding of the red cell cytoskeleton to the plasma membrane
- Due to mutation involving ankyrin, band 3 or spectrin proteins
What causes acquired spherocytosis?
- Usually caused by autoimmune hemolytic anemia
What do red blood cells look like in spherocytosis?
- They are round, smaller and have more intensely staining cytoplasm due to membrane loss and red cell dehydration
- Have elevated Mean Corpuscular Hemoglobin Concentration
What are the serum findings in hemolysis?
- Elevated lactate dehydrogenase
- Reticulocytosis
- Decreased Haptoglobin
What are the major clinical manifestations of Factor V laiden?
- Deep vein thrombosis
- Cerebral vein thrombosis
- Recurrent pregnancy loss
- 50% of patients with untreated DVTs will develop pulmonary embolism
What is Factor V laiden?
What risk does it lead to?
What does cause?
- Most common cause of inherited thrombophilia
- Heterozygote prevalence of 1-9% in caucasians
- 5-10 x the risk of developing thrombosis
- Homozygotes have 50-100X the risk of developing thrombosis
- Increased thrombin production due to decreased activated protein C
What does protein C do?
- It restricts clot formation
- Inactivates factors Va and VIIIa
- Factor Va is a cofactor for the conversion of prothrombin to thrombin
Which is a cofactor in the conversion of prothrombin to thrombin?
Factor Va
