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Flashcards in Hemolysis Deck (31)
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What are the 3 ways to become anemic?

1. lose RBCs
2. don't make enough RBCs
3. both


What are 2 ways to lose RBCs?

1. hemorrhage
2. hemolysis


What are the mechanisms of hemolysis?

-intravascular rupture of RBCs
-uptake of RBCs into macrophages in either the spleen or liver (reticuloendothelial system)


What lab values can detect hemolytic anemia?

-free hemoglobin in plasma and/or urine - not filtered by kidneys if overwhelmed by severe hemolysis
-LDH - lots released from lysed RBCs (*could also be due to lysis of other cells)
-unconjugated bilirubin - this end product of heme catabolism is normally removed by liver; turns serum yellow
-Haptoglobin - the hemoglobin recycler; it will be reduced (busy) when free Hgb levels are up
-Reticulocyte count - elevated due to compensatory increased red cell production


What findings on peripheral blood smear are indicative of compensatory RBC production?

-nucleated RBCs
-increased reticulocytes


What structural proteins, if mutated or defective, could result in loss of integrity of the RBC membrane and lead to hemolysis?

-anchors: Band 3
-cables: spectrin
-associated proteins: ankyrin


What are spherocytes and what test is done to diagnose?

spherocytes are RBCs that are sphere shaped instead of biconcave disc shaped because a genetic defect in structural proteins that results in the default most surface tension efficient shape; diagnosed by the osmotic fragility test


Describe the osmotic fragility test.

place RBCs in hypotonic solution and measure how many survive; if a high proportion burst (because they couldn't withstand the swelling) then the diagnosis is hereditary spherocytosis (or thalassemia)


Describe Hemoglobin crystallization. What disease is this significant in and how's it diagnosed?

RBCs have evolved to carry as much Hgb as possible--that is, very close to the crystallization concentration. Minor changes in Hgb can cause crystallization and RBC instability.
Disease = Hgb C disease
Diagnosis = Hgb electrophoresis


Describe polychromasia and what it indicates.

bluish discoloration of immature RBCs that are either reticulocytes or nucleated (nRBCs). Indicates that immature RBCs are being released from bone marrow which has increased production to compensate for anemia/rapid RBC loss


Describe the process and consequences of pyruvate kinase deficiency.

Without pyruvate kinase the RBC can't run glycolysis to make ATP which is needed for transporting Na+ out of / K+ into the cell to maintain the osmotic gradient. Upsetting the osmotic gradient will cause build up of Na+ within the cell, osmosis of water, and swelling/rupture of the RBC. (hence, anemia)


Describe G6PD deficiency.

Glutathione cleans up oxidative damage in RBCs by reducing oxidized proteins (like Hgb) and peroxide. To regenerate glutathione, NADPH must oxidize it. To generate NADPH the cell runs the pentose phosphate shunt pathway. G6PD is one of the first enzymes in this pathway. Without G6PD to run the pathway, NADPH can't be made and glutathione can't be regenerated; therefore the RBC dies of oxidative damage.


How does an individual usually first detect their G6PD deficiency?

hemolysis is observed following certain food intakes - especially fava beans


What are Heinz bodies?

precipitates of oxidized Hgb within RBCs that stain blue with methylene blue. They are there in patients with G6PD deficiency (because oxidized Hgb can't be repaired in such patients)


What is methemoglobinemia?

excessive oxidation of heme iron; can occur (along with hemolysis) in G6PD deficiency


If you have a patient with G6PD deficiency, what drug(s) should you not give them?

drugs that lyse RBCs - although there is little consensus about which ones those are. Ones that are agreed upon are dapsone and primaquine (used to treat malaria)


Describe paroxysmal nocturnal hemoglobinuria (PNH) and its diagnosis/treatment.

acquired non-malignant mutation in gene for PIG-A meaning no DAF/CD55 or protectin/CD59 will be anchored to the RBC surface. Thus the RBC is susceptible to destruction by the MAC complex.
Diagnose with flow cytometry (seeing no surface proteins).
Treat with allogenic bone marrow transplant and/or Ecluzimab (mAb against complement activation)


Name 4 bugs that lyse RBCs.

1. Malaria
2. Babesia
3. Bartonella
4. C. perfringens


What is the clinical presentation and pathophysiology of malaria?

Patient presents with high fever, dark urine, and jaundice after traveling to malaria-endemic area. This parasite is spread by mosquitos and results in lysis of RBCs after completing its life cycle within, using RBC contents.


What is the clinical presentation and pathophysiology of babesia?

protozoal intracellular parasite transmitted by ticks; endemic to NE US. Milder clinical course than malaria.


What is the clinical presentation and pathophysiology of bartonella bacilliformis?

Patient presents with fever, hemolytic anemia, and splenomegaly due to this facultative intracellular parasite that is endemic in northern Andes (and Colombia & Ecuador, transmitted by sand flies). Severe anemia seen in acute phase and cutaneous rash (warts) in chronic phase. Fatal unless treated with antibiotics


What is the clinical presentation and pathophysiology of clostridium perfringens?

C. perfringens secretes a toxin that can cause gas gangrene and hemolysis. The hemolysis doesn't always occur but when it does, it's severe and usually fatal.


Describe the pathophysiology of warm autoimmune hemolytic anemia (WAHA).

Autoimmune disease in which IgG antibodies (reactive at body temp 37˚C) against red cell surface antigens are produced. These can cause their uptake by macrophages mostly located in the spleen or liver; these macrophages can completely or partially clear the cells. It can also cause complement activation instead which may lead to either extravascular hemolysis aka phagocytosis via the C3 receptor on macrophages, or can lead to intravascular hemolysis by formation of MAC complex.


Describe the pathophysiology of cold autoimmune hemolytic anemia (CAHA).

a group of anti-RBC Abs (usually IgM) are cold-reactive (i.e., at 4-20˚C; sometimes called cold agglutinins) and can induce clumping of RBCs in the periphery (where it's colder than in the core). With luck that is all they do (may cause Raynauds) but can sometimes they initiate complement fixation and lead to hemolytic anemia


What are microspherocytes?

cells that are now spheres (instead of biconcave discs) because antibodies bound their surface and therefore macrophages take a bite out of them (instead of destroying them altogether) in an attempt to leave as much Hgb as they can


What are some major clues to the diagnosis of WAHA?

-evidence of hemolysis on serum testing (i.e., increased LDH, unconjugated bilirubin, increased haptoglobin)
-polychromasia (from increased hematopoiesis)
-basophilic stippling
-nucleated RBCs (from greatly accelerated RBC production in bone marrow)
-no blasts or myelocytes (differentiating the presence of nRBCs in WAHA from presence of nRBCs in other disease of bone marrow)
-lab testing of direct antiglobulin test (DAT, aka Direct Coomb's) to show Abs or complement already bound to RBC surface
-lab testing of antibody screen (aka indirect Coomb's test)


True or false: WAHA is present in up to 8% of hospitalized patients.

False - a positive DAT is seen in up to 8% of hospitalized patients. This does not necessarily indicate WAHA, but underscores the need to consider clinical and lab evidence of hemolysis, in addition to the results of the DAT/Ab screen tests.


What are some major clues to the diagnosis of CAHA?

-Raynaud's phenomenon
-evidence of hemolysis on serum testing (i.e., increased LDH, unconjugated bilirubin, increased haptoglobin)
-Red Cell agglutination (on peripheral blood smear)
-polychromasia (from increased hematopoiesis)
-basophilic stippling
-No blasts or myelocytes
**But keep in mind, EVERYONE had cold agglutinins when tested at 4˚C so you must consider clinical and lab evidence of anemia as well as eveidence of C3 on RBCs


Which is more often seen in association with malignancies: WAHA or CAHA?

WAHA (but CAHA is occasionally seen with malignancies too)


Describe thrombotic thrombocytopenic purpura (TTP), including pathophysiology, clinical presentation, and treatment.

Antibodies against AdamTS13 (protease) prevent it from cleaving vWF, so vWF stays too long and fibrin deposition/clot formation happens. This results in consumptive coagulopathy (thrombotic) in one place, and fewer platelets (thrombocytopenia) and bleeding elsewhere (purpura). The excess fibrin deposition damages RBCs by slicing them into schistocytes. This type of hemolysis is called microangiopathic.
Clinical evidence includes thromboses in brains and kidneys, low plts, hemolytic anemia, and purpura. Triad = fever, renal failure, fluctuating CNS symptoms.
Treat with plasmapharesis.