Flashcards in Heme/Onc2 Deck (50):
What is DIC?
Pathologic activation of the coagulation cascade, characterized by the consumption of both platelets and coagulation factors.
Widespread microthrombi result in ischemia and infarction.
What are the clinical manifestations/presentation of DIC?
bleeding, especially from IV sites and mucosal surfaces (bleeding from body orafices). Almost always secondary to a stimulus/other disease process
What are known triggers for DIC? (5)
(2) obstetric complications
(4) acute promyelocytic leukemia
(5) rattlesnake bite
Why do obstetric complications trigger DIC?
tissue thromboplastin in the amniotic fluid activates coagulation.
If the amniotic fluid were to leak into the mother's circulation, it could result in activation of the coag. cascase
What is tissue thromboplastin?
Also known as tissue factor, or factor III. This is a potent activator of the extrinsic pathway of the coagulation cascade.
Why do adenocarcinomas cause DIC?
Mucin (produced by the carcinoma) activates coagulation
Why does a rattlesnake bite tigger DIC?
venom activates coagulation
Why does acute promyelocytic leukemia cause DIC?
primary granules activated coagulation.
Why does sepsis cause DIC? With what microbes is this seen?
The endotoxins from bacterial walls and cytokines (e.g., TNF and IL-1) induce endothelial cells to produce tissue factor.
The is seen especially in sepsis with E. coli or N. meningitidis
What lab findings to we see in DIC? (5)
(1) decreased platelet count
(2) increased PT/PTT
(3) decreased fibrinogen
(4) microangiopathic hemolytic anemia
(5) elevated fibrin split products, particularly D-dimers
What are D-dimers
Fibrin split products derived from the splitting of cross-linked fibrin.
**D-dimer is not produced from splitting fibrinogen
What is the best screening test for DIC?
What is the treatment for DIC?
(1) addressing the underlying cause
(2) transfusing blood products and cryprecipitate as necessary
Why would we want to give cryoprecipitate to someone with DIC?
cryoprecipitate contains coagulation factors, which are being consumed in DIC
What test is used to measure prekallikrein?
What test is used to measure high molecular weight kininogen?
What test is used to measure fibrinogen?
TT (thrombin time)
On what cells is myeloperixidase stain used, and for what?
Used on neutrophils to diagnose myeloperoxidase deficiency.
This disease is clinically similar to chronic granulomatous disease
What is chromium-51 used to measure?
red cell survivial
What might an anti-Epstein-Barr virus stain be useful for?
in helping to prove that atypical lymphocytes on peripheral blood smear are probably due to infectious mononucleosis.
In what demographic group is hairy cell leukemia most often seen?
What should we think of if we observe a megaloblastic anemia in a person from the Great Lakes region after consuming poorly cooked fish?
B12 deficiency with resulting megaloblastic anemia is specifically associated with what infection?
What is the process of B12 absorption?
(1) salivary gland enzymes liberate vitamin B12, which is then bound by R-binder (also from the salivary gland) adn carried through the stomach to the small bowel
(2) pancreatic proteases in the duodenum detach B12 from R-binder
(3) B12 binds intrinsic factor in the small bowel; intrinsic factor-B12 complex is absorbed in the ileum.
What is the difference in onset of folate deficiency versus B12 deficiency, and why?
B12 deficiency is less common than folate deficiency, and takes years to develop, whereas folate deficiency develops within months.
This is because the body has minimal folate stores, whereas the body has large hepatic stores of B12
What is the most common cause of B12 deficiency?
What is pernicious anemia.
Autoimmune destruction of gastric parietal cells (in the body of the stomach) leads to an intrinsic factor deficiency--> impaired B12 absorption.
(The ileum recognizes/absorbs B12/IF complex, but not B12 alone. If the levels of IF decrease, the ileum will be unable to absorb B12--> deficiency.)
Besides pernicious anemia, what are other causes of B12 deficiency? (3)
(1) pancreatic insufficiency
(2) damage to the terminal ileum (e.g., Crohn disease, diphyllobothrium latum)
(3) dietary deficiency--rare, except in vegans
What are the clinical and lab findings in B12 deficiency? (6)
(1) macrocytic RBCs with hypersegmented neutrophils
(3) subacute combined degeneration of the spinal cord
(4) decreased serum B12
(5) increased serum homocysteine
(6) increased methylmalonic acid --> spinal cord damage
A 7 month old boy with failure to thrive is brought to the physician for a follow-up examination. His Hb is 4.4 g/dL. The PBS shows very small RBCs with marked palloe. Further evaluation shows low levels of HbA with elevated fractions of HbA2 and HbF. What is the underlying mechanism responsible for the findings in this patient?
This patient likely has beta thalassemia.
In beta thalassemia, a decrease in the production of globin --> a decrease in Hb --> microcytic anemia
What is thalassemia?
A microcytic anemia due to decreased synthesis of the globin chains of Hb:
decrease globin --> decrease Hb --> microcytic anemia
Against what disease are carriers of thalassemia protected?
Carriers are protected against Plasmodium Falciparum malaria
What would you see on peripheral blood smear with ß- thalassemia minor?
--microcytic, hypochromic RBCs
What would Hb electrophoresis show in ß- thalassemia minor?
When would ß thalassemia major present, and why does it present at this specific time?
Beta+ thalassemia typically presents at around 6 months of age. This is because for the first six months of life, HbF is still predominant and protective. However, after about six months, the predominant Hb switches to HbA, at which point infants become markedly anemic.
Why do we see increased HbA2 and HbF in ß-thalassemia major?
Production of these forms of hemoglobin increases to compensate for the diminished production of HbA
When would we see antibodies against fetal blood cells?
These are generally produced by a mother who has been sensitized to fetal blood antigens by transfusion or a previous pregnancy
What is the consequence of antibodies against fetal blood antigens?
Immune-mediated hemolysis--> intrauterine anemia and hydrops fetalis
What is hereditary spherocytosis?
Inherited defect of RBC cytoskeletal MB proteins, leading to normocytic anemia with extravascular hemolysis.
What is the basic pathogenesis of hereditary spherocytosis?
--membrane blebs are formed and lost over time
--loss of membrane renders cells round (spherocytes) instead of disc shaped
--spherocytes are less able to maneuver through the splenic sinusoids and are consumed by splenic macrophages, resulting in anemia
What do we see on PBS in hereditary spherocytosis? (3)
--spherocytes with loss of central pallor
--increased MCHC (mean corpuscular Hb concentration)
What are the clinical findings in hereditary spherocytosis?
--jaundice (inc. unconjugated bilirubin)
--increased risk for bilirubin gallstones
What complication are people with hereditary spherocytosis at increased risk for?
At increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors.
How is hereditary spherocytosis diagnosed?
Diagnosed by osmotic fragility test
This test reveals increased spherocyte fragility in hypotonic solution. (reduced MB and greater [Hb]--> greater cell swelling when placed in hypotonic solution)
What is the treatment for hereditary spherocytosis? Why?
splenectomy. This removes the site of peripheral/extravascular destruction: the splenic macrophages.
This will resolve the anemia
What is the consequence of splenectomy in hereditary spherocytosis? (What will show up on PBS?)
Howell-Jolly bodies with appear on peripheral blood smear. These are fragments of nuclear material in RBCs that are normally removed by splenic macrophages.
What cytoskeletal proteins are mostly commonly involved in hereditary spherocytosis?
A 3 month-old boy is brought to the emergency department by his parents because of yellowing of his skin. Physical examination shows pale palpebral conjunctiva, diffuse jaundice, and splenomegaly. A peripheral blood smear shows spherocytosis. The reticulocyte count is elevated. His parents state that two relatives have a similar condition. What is this boy's likely diagnosis? Which of the following is a complication?
He has hereditary spherocytosis.
He is at increased risk for bilirubin gallstones
A 3 month-old boy is brought to the emergency department by his parents because of yellowing of his skin. Physical examination shows pale palpebral conjunctiva, diffuse jaundice, and splenomegaly. A peripheral blood smear shows spherocytosis. The reticulocyte count is elevated. His parents state that two relatives have a similar condition.
Why is his reticulocyte count increased?
This boy has peripheral, extravascular destruction of his RBCs. However, he has no problem making RBCs. His bone marrow will respond by increasing RBC synthesis, which will lead to an increase in the corrected reticulocyte count to >3%.