DIT review - Heme 1 Flashcards
What steps of the coagulation cascade do Protein C and S work on?
Protein C inhibits the activating factors VIII and V
Protein S is a cofactor for Protein C
What is responsible for the activation of Kallikrein
- Factor XIIa converts prekalikrein to kallikrein
What are the 2 functions of kallikrein
- Kallikrein cleaves plasminogen to plasmin
- Plasmin breaks down the fibrin mesh
- So factor XIIa is a regulator to make sure the coagulation cascade doesn’t go too crazy
- Kallikrein converts high molecular weight kininogen (HMWK) to bradykinin
What is the function of bradykinin
- Bradykinin has 3 functions:
- Vasodilation
- Increased vascular permeability
- Pain mediator
- This is why coagulation and inflammation are interconnected’
- ACE is responsible for degrading bradykinin
- So bradykinin can cause angioedema in patients taking ACEI
- ACE is responsible for degrading bradykinin
What are the deficient factors in Hemophilia A, B, and C
- Hemophilia A
- Deficiency of factor VIII
- Increases PTT (no effect on PT or INR)
- Hemophilia B
- Deficiency of factor IX
- Increases PTT (no effect on PT or INR)
- Hemophilia C
- Deficiency of factor XI
- Increases PTT (no effect on PT or INR)
Describe the role of Vitamin K in the coagulation cascade, including the Vitamin-K dependent factors
- Vitamin K acts as a cofactor to gamma glutamyl transferase in the liver for activation of certain factors
- Vitamin K must first be reduced by liver epoxide reductase
- Warfarin inhibits epoxide reductase
- Vitamin K must first be reduced by liver epoxide reductase
- Vitamin K-dependent factors:
- Factors II, VII, IX, X, C, and S
- THINK: diSCo started in 1972
What is the defect in Factor V Leiden
- Mutation that makes Factor Va resistant to inactivation by protein C
- Guanine to Adenosine point mutation
- Increased coagulation
Describe prothrombin mutation
- Prothrombin G20210A mutation
- Mutation on prothrombin gene causes increased production of prothrombin (II)
- Predisposes to thrombosis
Describe Anti-thrombin defiency
- Unable to inactivate thrombin
- Patients often resistant to Heparin, or must be given a larger dose
Describe Protein C and S deficiency
- Unable to inactivate factors V and VIII
Describe the pathophysiology behind Heparin-induced thrombocytopenia
- Heparin binds to platelet factor 4
- Antibodies form against this complex
- Antibody-heparin-PF4 complex can then destroy platelets, and their fragments will activate remaining platelets
- Leads to thrombocytopenia and hypercoagulable state
What is the MOA of Heparin
Binding and activation of Anti-thrombin III, so that there is inactivation of thrombin (II) and factor X
What drug is used to reverse the effects of Heparin
Protamin sulfate (Sketchy = protected area)
It is positively charged and will bind to negatively-charged Heparin, and inhibit it
What is the suffix of LMWH drugs?
“-parin”
What is the difference between Unfractionated heparin and LMWH
LMWH only increases inhibtion of Factor X, not thrombin (II)
LMWH effects are not inhibited by protamine sulfate
LMWH has greater bioavailability and longer half life
Does not require PTT monitoring
What is basophilic stippling and what diseases is it seen in
- Small dots in the periphery of erythrocytes = visualization of ribosome aggregation in cytoplasm of RBCs
- Seen in:
- Lead poisoning
- Thalassemias
- Myelodysplastic syndrome
What are acanthocytes (“spur cells”) and what diseases are they seen in
- “Spur cells” - cells with irregular spikes (vs. echinocytes)
- Seen in states of cholesterol dysregulation:
- liver disease, abetalipoproteinemia
What are echinocytes (“burr cells”) and what disease are they seen in?
- RBCs
- “Burr cells” – uniform projections (vs. Acanthocytes)
- Seen in renal failure
What are dacrocytes and what disease are they seen in?
- RBC
- “Teardrop cell”
- Seen in bone marrow infiltration (e.g. myelofibrosis)
What is the cause of Heinz bodies and bite cells and what disease are they associated with?
- Due to Glucose-6-phosphate dehydrogenase (G6PD) Deficiency
- No NADPH created in order to reduce glutathione, which is needed to protect RBCs from oxidative damage
- Heinz bodies are precipitated hemoglobin within the RBC
- Bite cells are due to the phagocytic removal of bite cells
What disease are elliptocytes associated with>
- RBC “pencil cell”
- Dye to Hereditary elliptocytosis
What are ringed sideroblasts and what disease are they found int?
- Nucleated RBC precursor with granules of iron in mitochondria
- Found in the bone marrow
- Due to sideroblastic anemia
What is a schistocyte and what diseases is it associated with?
- Fragmented (sheared) RBC
- E.g. Helmet cell
- Due to DIC, TTP/HUS, HELLP syndrome, mechanical hemolysis
What is a target cell and what causes it?
- Due to bleb of membrane allowing hemoglobin to build up in the center of cell
- Cause by either decreased cytoplasm or increased membrane
- Causes: HALT
- HbC disease
- Asplenia
- Liver disease
- Thalassemia
What are Howell Jolly bodies and what causes them?
- Basophilic nuclear remnants found in RBCs
- Can only be one in each RBC because there can only be one nucleus
- Seen in patients with hyposplenia or asplenia
