Red cell diseases and bleeding disorders - Practice Flashcards

A comprehensive set of Q&A flashcards covering anemia classifications, mechanisms, specific diseases (hemolytic anemias, HS, G6PD deficiency, SCD, thalassemias, megaloblastic anemias, iron metabolism), bleeding disorders, and transfusion-related complications based on the provided lecture notes.

What is anemia?

A reduction of the total circulating red cell mass below normal limits (often defined by a decreased hematocrit).

What does hematocrit measure?

The ratio of packed red blood cells to total blood volume.

What does MCV stand for and what does it measure?

Mean cell volume; the average volume of a red blood cell, expressed in femtoliters (fL).

What does MCH stand for and what does it measure?

Mean cell hemoglobin; the average content (mass) of hemoglobin per red cell, expressed in picograms (pg).

What does MCHC stand for and what does it measure?

Mean cell hemoglobin concentration; the average concentration of hemoglobin in packed red cells, expressed in g/dL.

What does RDW represent?

Red cell distribution width; the coefficient of variation of red cell volume. A high RDW indicates increased variation in red blood cell size (anisocytosis) and is commonly seen in iron deficiency anemia.

List examples of microcytic anemias.

Thalassemias; anemia of chronic illness; iron deficiency (late); lead poisoning.

What defines normocytic anemia in terms of MCV?

MCV 80–100 fL.

Give examples of normocytic anemias.

Hemolytic (high reticulocyte index); nonhemolytic causes include iron deficiency (early), anemia of chronic disease, aplastic anemia, CKD, acute blood loss.

List examples of megaloblastic macrocytic anemias

Folate deficiency; vitamin B12 deficiency; Fanconi anemia.

list examples of non-megaloblastic macrocytic anemias

Liver disease; chronic alcohol overuse; Diamond-Blackfan syndrome.

What happens in acute blood loss to blood volume and hematocrit?

Decreased intravascular volume with potential cardiovascular collapse; hemodilution lowers hematocrit.

What compensatory mechanism follows acute blood loss?

Increased erythropoietin from kidney stimulates marrow to produce more red cells.

What are the typical red cell features after acute blood loss?

Red cells are normocytic and normochromic;

reticulocytosis occurs as marrow responds (this is a normal bodily response to hypoxia)

What is extravascular hemolysis?

Premature destruction of red cells in macrophages, especially in the spleen, due to reduced deformability.

The RBC itself is fine, but the body is reacting improperly

What is intravascular hemolysis?

Hemolysis that occurs within the vasculature due to mechanical injury, complement fixation, infection, or toxins.

RBC has something wrong with it that causes the body to react to it

What are the main clinical features of extravascular hemolysis?

Anemia, splenomegaly, and jaundice.

Which test is used to diagnose PNH?

Flow cytometry detecting loss of GPI-anchored proteins (e.g., CD55, CD59) on blood cells.

What is the consequence of splenectomy in extravascular hemolysis?

Often beneficial by reducing sequestration and destruction of sensitized erythrocytes.

What inheritance pattern and membrane defect characterize hereditary spherocytosis (HS)?

Autosomal dominant; defects in spectrin, ankyrin, band 4.1, or band 4.2 leading to spherical, less deformable red cells in the peripheral smear.

These spherical cells (spherocytes) get trapped in the spleen where they are picked up by macrophages.

What is a key diagnostic test for Hereditary Spherocytosis and what does it show?

Osmotic fragility test; increased fragility of spherocytes in hypotonic saline.

Spherocytes cannot withstand hypotonia, they will rupture.

What happens to MCHC in hereditary spherocytosis?

MCHC is increased due to dehydration from loss of potassium and water.

Which does G6PD deficiency predispose RBCs to (how does it cause anemia)

Deficiency of glucose-6-phosphate dehydrogenase (G6PD) predisposes to episodic hemolysis due to oxidative stress. There is a lack in the shunt that normally protects the RBCs.

Why are G6PD deficiency populations at higher risk?

G6PD deficiency is more prevalent in people of African descent and in the Mediterranean due to historical malaria selection.

What are Heinz bodies and when do they appear?

Dark inclusions in red cells formed by denatured hemoglobin; seen after oxidative stress in G6PD deficiency.

What mutation causes sickle cell disease (SCD)?

Missense mutation in the β-globin gene substituting valine for glutamic acid at position 6.

Compare the normal adult Hb type to that of someone with Sickle cell

in a normal adult red cell, the Hb is mainly HbA, with small amounts of HbA2 and HbF.

In sickle cell, almost all the red cell is HbS

How does HbF affect sickling?

HbF inhibits polymerization of HbS, reducing sickling; higher HbF leads to milder disease.

What factors promote sickling in deoxygenated conditions?

High intracellular HbS concentration (high MCHC), low intracellular pH, longer transit time in microvasculature (e.g., spleen, bone marrow), and inflammation.

What is Acute Chest Syndrome (ACS) in sickle cell disease (SCD)?

Acute Chest Syndrome (ACS) is a severe complication of sickle cell disease characterized by a new pulmonary infiltrate on chest X-ray accompanied by fever and/or respiratory symptoms (e.g., chest pain, wheezing, cough, tachypnea, dyspnea, hypoxia). It is a leading cause of morbidity and mortality in SCD, often triggered by vaso-occlusion, fat emboli, or infection.

What is the classic bone change seen in SCD on radiology?

Crewcut appearance due to marrow expansion from extramedullary hematopoiesis.

Which two globin genes are implicated in thalassemia and where are they encoded?

Beta-globin gene on chromosome 11; alpha-globin genes on chromosome 16.

What are the primary pathological effects of impaired β-globin synthesis in beta-thalassemia?

Impaired β-globin synthesis results in an excess of unstable αα-globin chains. These chains precipitate, causing premature death of red cell precursors (ineffective erythropoiesis) and destruction of mature red cells (hemolysis), leading to anemia and hypochromic microcytic red cells.

What abnormal cells are seen in peripheral smear with Beta-Thalassemia?

target cells, basophilic stippling cells, and nucleated RBCs

What is the cause of hydrops fetalis in alpha-thalassemia?

Deletion of all four alpha-globin genes; fetus has severe anemia and hydrops; requires transfusion and may be curable with stem cell transplant.

What is the hallmark of paroxysmal nocturnal hemoglobinuria (PNH)?

Acquired PIGA mutation leading to loss of GPI-anchored proteins (CD55 - decay accelerating factor, C8-biniding protein, and CD59 - reactive lysis) and intravascular hemolysis; high risk of venous thrombosis.

most common is CD59 which is normally a strong inhibitor of MAC in complement

What is the distinguishing haemolysis pattern in PNH?

Intravascular hemolysis due to absence of GPI-anchored complement regulators.

also RBC lysis at night due to a slight decrease in pH

what is the triad of symptoms in paroxysmal nocturnal hemoglobinuria

Coombs negative hemolytic anemia

pancytopenia

venous thrombosis (budd-chiari syndrome)

What is megaloblastic anemia and what is its cause

impaired DNA synth due to a decrease in B12 and/or folate

Vitamin B12 deficiency leads to what?

decreased FH4 and conversion of homocysteine to methionine, leading to decreased DNA synth

Explain the relationship between folate and B12 in B12 deficiency

though lack of folate is the primary cause of anemia in B12 deficiency, treating with folate will actually worsen neurological symptoms

Folate treatment will improve the anemia symptoms, BUT

B12 is still needed because it is required for converting methyl CoA to succinyl CoA

What is the presentation for Megaloblastic anemia

hypercellular marrow and increased growth factors such as erythropoietin

pernicious anemia MOA and what happens

autoimmune gastritis impairing the production of intrinsic factor. so B12 cannot be absorbed

loss of parietal cells from the fundus

What is immune thrombocytopenic purpura (ITP)?

Autoantibody-mediated destruction of platelets (IgG against platelet glycoproteins IIb-IIIa or Ib-IX); splenic sequestration and phagocytosis of opsonized platelets.

levels of homocysteine and methylmalonic acid in B12 and folate deficiency

B12 deficiency:

• elevated homocysteine and methylmalonic acid

folate deficiency

• homocysteine levels are increased, methylmalonate concentrations are normal

What are the two main HIT types and their characteristics?

Type I: a rapid, non-immune platelet decrease beginning after heparin treatment

Type II: immune-mediated, occurs 5–14 days after heparin, with risk of venous/arterial thrombosis; avoid heparins (use alternatives). less common but more serious

What are thrombotic microangiopathies (TTP/HUS) characterized by?

excessive platelet activation leading to thrombosis. microangiopathic hemolytic anemia; thrombocytopenia

PT/PTT usually normal.

How do TPP and HUS differ in their presentation

in addition to thrombocytopenia, microangioipathic hemolytic anemia, and fever, TPP has neurological symptoms and renal failure

HUS doe not have these additional things

What enzyme deficiency defines TTP?

Deficiency of ADAMTS13 (vWF metalloprotease) leading to large vWF multimers and platelet aggregation.

What toxin is classically linked to typical HUS?

Shiga-like toxin from Escherichia coli O157:H7 causing endothelial damage and microangiopathy.

What is a key difference between TTP and HUS in labs?

TTP: PT and PTT usually normal; HUS: similar, but may have different clinical emphasis (often pediatric with renal involvement in HUS).

What are common laboratory tests to assess bleeding disorders?

Prothrombin time (PT), Partial thromboplastin time (PTT), platelet count, platelet aggregation, and von Willebrand factor tests.

What causes DIC (disseminated intravascular coagulation)?

Systemic activation of coagulation with consumption of platelets and coagulation factors

triggers include obstetric complications, sepsis, malignancy, and trauma

What are typical findings in DIC?

Low fibrinogen, prolonged PT and PTT, elevated D-dimers; widespread microthrombi and organ ischemia.

What are key signs and symptoms for aplastic anemia?

Chronic hematopoietic failure and pancytopenia.

Also hypocellular bone marrow lacking hematopoietic elements (dry tap)

What is pure red cell aplasia?

a marrow disorder where erythroid progenitors are the only ones suppressed

What is the presentation of anemia of chronic inflammation (ACI)?

Low serum iron, low total iron binding capacity, high ferritin

what are the 3 categories in anemia of chronic inflammation

chronic microbial infections

chronic immune disorders

neoplasms

How does hepcidin regulate iron metabolism in inflammation?

Hepcidin binds ferroportin which inhibits it, thus iron can’t be transferred from the storage pool

Where is most body iron stored and in what form?

Ferritin and hemosiderin; main storage sites in liver and macrophages.

What is the role of transferrin in iron transport?

Transferrin carries iron in plasma to cells (normally about one-third saturated with iron)

What is Prussian blue staining used for in iron studies?

Detects iron in tissue as blue iron-containing granules in ferritin/hemosiderin; used in liver and marrow samples.

What happens to ferritin and transferrin saturation in iron deficiency?

Low ferritin and low transferrin saturation; RDW often high; ferritin correlates with iron stores.

What hormone regulates iron absorption in the duodenum?

Hepcidin; high hepcidin decreases iron absorption, low stores increase absorption.

What are classic signs of iron deficiency anemia on exam and history?

Koilonychia (spoon nails), glossitis, angular cheilosis; pica; Plummer-Vinson syndrome (esophageal webs and glossitis).

What are characteristic megaloblastic changes in bone marrow and blood?

Hypercellular marrow with megaloblasts, hypersegmented neutrophils, macrocytosis and oval macrocytes in blood smear.

What is the difference between pernicious anemia and other B12 deficiency causes?

Pernicious anemia is autoimmune destruction of intrinsic factor-producing cells leading to B12 malabsorption.

Has an increased risk of gastric carcinoma.

Why can folate deficiency mimic B12 deficiency clinically but differ neurologically?

Both cause megaloblastic anemia, but folate deficiency lacks B12-related neurologic findings

What is a key lab feature distinguishing B12 vs folate deficiency?

Elevated methylmalonic acid is specific for B12 deficiency, while both deficiencies raise homocysteine.

What is the consequence of B12 deficiency on myelin?

Myelin breakdown and subacute combined degeneration of the spinal cord due to methylmalonic acid accumulation.

What is the mechanism by which pernicious anemia increases gastric cancer risk?

Chronic autoimmune gastritis with intestinal metaplasia and parietal cell loss increases gastric cancer risk.

What are the two major storage and transport regulators for iron?

Ferritin stores iron, transferrin transports iron in plasma.

What are the key features of thalassemias?

Genetic disorders with reduced synthesis of either α- or β-globin chains; imbalance causes ineffective erythropoiesis and hemolysis; crew-cut bones from marrow expansion in severe cases.

Where are α-globin and β-globin genes located?

α-globin genes on chromosome 16; β-globin gene on chromosome 11.

What would you expect on blood smear in beta-thalassemia major?

Anisocytosis, poikilocytosis, microcytosis, hypochromia; target cells; basophilic stippling; elevated reticulocyte count.

What is HbH disease?

Beta-thalassemia-like syndrome caused by deletion of three α-globin genes, forming HbH (β4) tetramers.

What is Hb Bart’s and when is it seen?

Gamma tetramers (Hb Bart’s) seen in newborns with severe α-thalassemia (all four alleles deleted).

What makes hydropic fetalis severe and how is it managed?

All four α-globin genes deleted; fetus has high-oxygen affinity gamma tetramers with poor tissue delivery; transfusions and possibly stem cell transplantation are used; fetal prognosis poor without intervention.

What is Paroxysmal nocturnal hemoglobinuria (PNH) triad?

Coombs-negative hemolytic anemia; pancytopenia; venous thrombosis (often Budd-Chiari syndrome).

What is a major therapeutic option that reduces hemolysis and thrombosis in PNH?

C5 complement inhibitor eculizumab.

What is the direct Coombs test used for?

Direct antiglobulin test to detect antibodies or complement on patient’s red cells.

What characterizes warm autoimmune hemolytic anemia (AIHA)?

IgG antibodies reactive at body temperature causing extravascular hemolysis; positive direct Coombs test.

What characterizes cold agglutinin disease?

IgM antibodies bind red cells at low temperatures (0–4°C) causing intravascular hemolysis and vascular symptoms; avoid cold exposure.

more localized to peripheral limbs and digits

What is a common laboratory feature of immunohemolytic anemia?

Positive Coombs test (direct antiglobulin test) indicating antibodies or complement on red cells.

What are megaloblastic changes a hallmark of, and what are the two main vitamin deficiencies?

Megaloblastic anemia from impaired DNA synthesis; vitamin B12 (cobalamin) and folate deficiencies.

What is pernicious anemia and its significance?

Autoimmune gastritis causing intrinsic factor deficiency leading to B12 deficiency; increases risk for gastric cancer.

What is the role of intrinsic factor?

Intrinsic factor is required for intestinal absorption of vitamin B12 in the ileum.

What lab markers indicate B12 deficiency vs folate deficiency?

B12 deficiency: low B12, elevated homocysteine and methylmalonic acid

folate deficiency: elevated homocysteine, normal methylmalonic acid.

What is the classic explanation for iron deficiency anemia pathogenesis?

Inadequate Hb synthesis due to iron deficiency leading to hypochromic microcytic anemia.

What are typical iron deficiency lab findings?

Low serum iron, low ferritin, low transferrin saturation; high TIBC; low RDW with iron deficiency usually, but RDW often high.

What is hepcidin’s role in iron regulation?

Hepcidin inhibits ferroportin, decreasing iron export from enterocytes and macrophages, reducing plasma iron.

What is the classic radiographic bone change in severe iron deficiency anemia?

May show spoon-shaped nails and, in long-standing cases, bone changes with marrow space alterations; not specific on radiographs.

What is the typical cause and presentation of anemia of chronic inflammation (ACI)?

Anemia seen in chronic inflammatory states; low serum iron with high ferritin and low TIBC due to hepcidin-mediated iron sequestration.

What distinguishes aplastic anemia from other anemias?

Pancytopenia with hypocellular marrow lacking hematopoietic elements (dry tap) often after drugs, chemicals, or infections.

What is polycythemia vera?

Primary polycythemia due to clonal proliferation of erythroid precursors; increased red cell mass; can be due to JAK2 mutations.

What is the triad of the hemostasis system?

Vessels, platelets, coagulation cascade.

Which tests assess the extrinsic and common coagulation pathways?

Prothrombin time (PT). Prolonged PT suggests deficiency/dysfunction of factors II, V, VII, X, fibrinogen.

Which tests assess the intrinsic and common coagulation pathways?

Partial thromboplastin time (PTT). Prolongation suggests deficiency/dysfunction of factors VIII, IX, XI, XII, V, X, prothrombin, fibrinogen.

What laboratory test assesses platelet quantity?

Platelet count measured on anticoagulated blood.

What test evaluates platelet function in terms of adhesion?

Platelet aggregation testing and von Willebrand factor assays.