Pathoma Ch. 4 - Blood Flashcards
4 steps of primary hemostasis (w/ molecular causes)
- Vasoconstriction (reflex neural stim., ENDOTHELIN)
- Platelet adhesion (Collagen + vWF + Gp1b)
- Degranulation (ADP, TxA2)
- Aggregation (2b/3a + fibrinogen)
Functions of ADP and TxA2 from platelet degranulation
ADP – promote exposure of 2b/3a receptor
TxA2 – promote aggregation
Petechiae = ____ (NOT ___)
Thrombocytopenia (NOT qualitative disorder)
Purpose of giving IVIg
Compete with the actual problematic antibodies for the splenic macrophages –> reduce splenic hemolysis
ITP - where do antibodies come from?
Plasma cells in the spleen
TTP - why is ADAMTS13 deficient?
Acquired autoimmune antibody to it
HUS - why the symptoms? (3)
Verotoxin (Shiga-like toxin) causes endothelial cell damage –> thrombus formation in the kidney small vessels
Thrombi –> consumes platelets –> petechiae
Thrombi –> mechanical destruction of RBCs –> hemolytic anemia + schistocytes
TTP - why the neuro symptoms?
Thrombi form in small vessels of brain
Treatment for HUS and TTP
Plasmapheresis (remove antibodies)
Corticosteroids (stop antibody synthesis)
Qualitative platelet disorder + enlarged platelets
Bernard-Soulier (“Big Suckers”)
How does uremia affect platelet function?
Disrupts adhesion AND aggregation
Function of the coagulation cascade
What happens after that?
Produce thrombin, which converts fibrinogen to fibrin in the platelet plug
Fibrin is cross-linked –> STABLE
How to tell if clotting factor is deficient or being destroyed by antibodies?
Deficient –> mixing study corrects it
Antibodies –> mixing study does NOT correct it
Epoxide reductase
Activator of Vitamin K in the liver
Function of Vitamin K
What does that mean?
Gamma-carboxylation of factors 2, 7, 9, 10, C and S
Allows for CALCIUM to bind
Hemorrhagic disease of the newborn
Vitamin K deficiency (no gut bacteria)
Effect of liver failure on coagulation is measured via ___
PT
Function of Protein C
Function of Protein S
Function of Antithrombin 3
C = inhibit 5 and 8 S = activate C (w/ thrombomodulin) AT3 = inhibit 10 and 2 (thrombin)
HIT…explain
What to watch for?
What NOT to give? Why?
Heparin binds to PF4 on platelets
The body creates antibodies against these complexes
The spleen destroys the complexes (thrombocytopenia)
Platelet bits into circulation –> activation of others –> THROMBOSIS
Warfarin (risk of warfarin skin necrosis)
Warfarin skin necrosis…explain
Tie in w/ HIT?
Warfarin –> decreased Protein C and factor 7 FIRST –> increased coaguability –> blood clots in skin vessels
HIT –> thrombosis risk –> Warfarin INCREASES thrombosis risk –> tissue necrosis
Rattlesnake bite –> starts bleeding
Venom –> activates clotting cascade –> DIC
Sepsis –> bleeding from everywhere
Endotoxin + TNF/IL-1 –> endothelial cells express tissue factor –> DIC
Obstetric complication –> bleeding from everywhere
Tissue thromboplastin in the amniotic fluid
D-dimer comes from where?
Splitting of CROSS-LINKED fibrin
Functions of plasmin
What inactivates it?
- Cleave fibrin
- Destroy serum fibrinogen
- Block platelet aggregation
Alpha-2 anti-plasmin (serum protease inhibitor)
Radical prostatectomy –> excess bleediing
Release of UROKINASE activates plasmin
Bleeding everywhere Increased PT/PTT Increased bleeding time Normal platelet count Normal qualitative studies No D-dimer
Treatment?
Plasmin overactivation (cirrhosis, prostatectomy)
Tx = Aminocaproic acid (blocks plasminogen activation)
Lines of Zahn
Other way to distinguish from post-mortem clot
Alternation of platelets/fibrin w/ RBCs
Attachment to vessel wall
Anti-thrombotic functions of endothelial cells (5)
- Block exposure to collagen and tissue factor
- PGI2 and NO –> vasodilation and inhibited aggregation
- Heparin-like molecules –> enhanced AT3
- tPA
- Thrombomodulin
Describe the interaction between folate, B12, and homocysteine
Why is this important? (the homocysteine part)
- THF circulates as methyl-THF
- Methyl transferred to B12 –> THF drives thymidylate synthase (dTMP production)
- Methyl transferred to homocysteine –> converted to methionine
Elevated homocysteine = THROMBOSIS via endothelial cell damage
Long, slender fingers, lens dislocation, mental retardation, vessel thrombosis
Explain
Homocysteinuria
CBS deficiency (or B6 deficiency)
Prothrombin 20210A
Inherited point mutation in prothrombin –> increased gene expression –> increased coagulation
OCP hypercoaguability
Estrogen –> increased coagulation factor production
Laparascopic surgery –> respiratory distress
Gas embolus (air pumped into abdomen)
Amniotic fluid embolus – finding?
Squamous cells and keratin debris in the embolus
What is required for a PE to cause symptoms?
Infarction of large or medium artery + pre-existing cardiopulmonary compromise (usually)
PE – pathology
Hemorrhagic, wedge-shaped infarct
Microcytic anemias (4)
Iron deficiency Anemia of chronic disease (functional deficit of iron) Sideroblastic anemia (deficit of protoporphyrin) Thalassemia (deficit of globin)
Absorption location of…
- Iron
- Folate
- B12
Iron = duodenum Folate = jejunum B12 = ileum
Gastrectomy –> iron deficiency
Acid keeps iron in 2+ state (“goes 2 the blood”)
Functions of hepcidin (2)
- Sequester iron, limiting transfer to RBCs
- Suppress EPO
Increased free erythrocyte protoporphyrin
Iron deficiency of some kind
Alpha vs. Beta thalassemia – genetics
Alpha = gene DELETION Beta = gene MUTATION (promotor or splice site)
Microcytic, hypochromic RBCs
Increased RBC count
Target cells
Increased HbA2 and HbF
What causes target cells? (in general) (2)
Beta-thalassemia minor
Decreased cytoplasm OR increased membrane
Microcytic, hypochromic anemia as an infant
Crewcut x-ray
Chipmunk facies
HSM
Increased risk for what? (2)
Beta-thalassemia major
Infusion-induced hemochromatosis Aplastic crisis (B19)
Beta-thalassemia major – see what on blood smear
Target cells
Nucleated RBCs
Beta-thalassemia major - Hb type(s)?
Increased HbA2 and HbF
Macrocytic anemia w/o megaloblastic change (3)
- Alcoholism
- Liver disease
- 5-FU (ex.)
Folate vs. B12 deficiency - time frame
Folate - months
B12 - years
Causes of folate deficiency (6)
- Alcoholic (poor diet)
- Elderly (poor diet)
- Pregnancy (demand)
- Cancer (demand)
- Hemolytic anemia (demand)
- Methotrexate (inhibition)
Describe pathway of B12 absorption (5)
- Amylase liberates it
- Bound by R-binder
- Proteases in duodenum detach it
- B12 binds IF in small bowel
- B12-IF complex absorbed in terminal ileum
Causes of B12 deficiency (5)
- Pernicious anemia
- Pancreatic insufficiency (no protease to detach it)
- Crohn’s disease (ileum damage)
- D. latum (ileum damage)
- Vegans (dietary)
Larger RBCs with bluish cytoplasm
Reticulocytes (residual RNA)
How to determine true reticulocyte count?
Why?
What do the results mean?
RC x Hct/45
Anemia –> FALSE increased reticulocyte value
3+% = good marrow response (destruction)
Under 3+ = poor marrow response (underproduction)
Normocytic anemia + extravascular hemolysis (3)
Hereditary spherocytosis
Sickle cell anemia
Hemoglobin C
Normocytic anemia + intravascular hemolysis (5)
PNH G6PD deficiency Immune hemolytic anemia Microangiopathic hemolytic anemia Malaria
Sickle cell - increased risk of sickling (3)
Acidosis
Dehydration
Hypoxemia
Intravascular hemolysis in sickle cell
See what on blood smear?
Damaged membrane due to sickling –> DEHYDRATES –> hemolysis, decreased haptoglobin, etc.
TARGET CELLS (dehydration)
Sickle cell + gross hematuria and proteinuria
Renal papillary necrosis
Microscopic hematuria, some HbS found
Sickle cell trait (only sickles in renal medulla)
Metabisulfite test
Any amount of HbS –> sickling
Positive in the disease OR the trait
Hemoglobin C - cause
See what on blood smear?
Glu –> Lys mutation (causes MORE positive charge)
HbC crystals
PNH - deficiencies
No GPI –> no DAF –> no inhibitor of C3 convertase
PNH - 3 tests for diagnosis
- Sucrose test
- Acidified serum test
- Flow cytometry for CD55 (DAF)
Death in PNH
Thrombosis of hepatic, portal, or cerebral veins
**2 complications of PNH
- Iron deficiency anemia (chronic hemolysis)
- ***AML
Causes of IgG immune hemolytic anemia (5)
SLE, CLL, Penicillin, Cephalosporins, Alpha-methyldopa
Causes of IgM immune hemolytic anemia (2)
Mycoplasma, Infectious Mononucleosis
IgG vs. IgM immune hemolytic anemia – hemolysis
IgG = extravascular IgM = intravascular
