RBC pathology Flashcards
What are the typical clinical findings of anemia?
Pale, weak, malaise, easily fatigued, dyspnea on exertion, and SOB
How quickly are reticulocytes produced?
5 days
What are some long-term effects of chronic anemia and hypoxia?
fatty changes to liver, myocardium and kidneys
What are the effects of acute blood loss anemia?
A shift of interstitial fluid to intravascular – this lowers hematocrit
Increased EPO production
Iron deficiency
Leukocytosis (for significant blood loss)
Reticulocytosis and thrombocytosis (days after blood loss)
What are the key features of all hemolytic anemias?
Shortened RBC life span (<120 days)
Elevated EPO
Accumulation of hemoglobin degredation products (unconj. bilirubin)
Hereditary spherocytosis
RBC vulnerable to splenic destruction due to sphere shape AD disorder increased MCHC *anemia, splenomegaly and jaundice* aplastic crisis = parvovirus hemolytic crisis = mono tx: splenectomy
G6PD deficiency
episodic hemolysis caused by oxidative stress – infections, drugs or food
micro pathology = Heinz bodies and bite cells
Sickle cell disease
Glu –> Val mutation
hemolytic anemia, microvascular obstructions and ischemic tissue damage leading to a variety of “crises”
SS vaso-occlusive crisis
hypoxic injury and infarction that cause pain in affected region
most severe = acute chest crisis (lungs)
SS sequestration crisis
massive entrapment of sickle cells leading to splenic enlargment, hypovolemia and sometimes hypovolemic shock
SS aplastic crisis
infection of RBC progenitors by parvovirus B19 causing transient cessation of erythropoiesis and sudden worsening of anemia
Hemoglobin C disease
mild hemolytic anemia
mechanism similar to SS but hemoglobin C does not sickle as readily as hemoglobin S
Beta-thalassemia major
deficient HbA synthesis resulting in microcytic hypochromic RBC with abnormal O2 transport
ineffective erythropoiesis
RBC prone to splenic destruction
HbF markedly elevated
poor clinical discourse without blood transfusion and iron chelation
hepatosplenomegaly due to extramedullary hematopoiesis
Mediterranean, African and Asian descent
Beta-thalassemia minor
patients are asymptomatic
if present, anemia is mild
hypocromic and microcytic (looks like iron deficiency anemia)
increased HbA2 but normal HbF
Mediterranean, African and Asian descent
Alpha-thalassemia
reduced or absent synthesis of alpha-globin chains
complete abscence is lethal in-utero
hemolysis and ineffective erythropoiesis less severe than beta-thalassemia
newborns = hemoglobin Barts
children and adults = Hbh
paroxysmal nocturnal hemoglobinuria (PNH)
acquired mutation of PIGA gene
susceptible to intravascular hemolysis by complement
typically chronic hemolysis without hemoglobinura despite name
prone to thrombosis
Immunohemolytic anemias
caused by antibodies against normal RBC constituents or antigens modified by haptens
results in either extravascular hemolysis or uncommonly complement fixation/intravascular hemolysis
hemolytic anemia from trauma to RBC
usually occurs in individuals with cardiac valve prostheses (mechanical) and microangiopathic disorders
vascular changes produce shear stresses than injury circulating RBC
megaloblastic anemias
caused by folate or cobalamin deficiency leading to impairment of DNA synthesis
macrocytic morphology
pernicious anemia
type of megaloblastic anemia caused by autoimmune gastritis that impairs production of IF required for B12 uptake
autoreactive T-cells initiates gastric mucosal injury and triggers formation of IF autoantibodies
leukopenia, elevated homocysteine and elevated methymalonic acid
B12 deficiency
type of megaloblastic anemia caused by impaired absorption of B12 due to loss of pepsin secretion, gastrectomy, ileal resection or certain tapeworms
elevated homocysteine and methymalonic acid
Folate deficiency
type of megaloblastic anemia caused by insufficient diet
elevated homocysteine but normal MMA
porphyria
a deficiency in the pigments involved in the formation of heme (porphyrins) which causes anemia and/or splenomegaly
abnormal reaction to sunlight, abnormal hair growth, teeth staining, seizures, hallucinations, and general psychosis
vampires and werewolves
iron deficiency anemia
most commonly due to chronic blood loss morphologically microcytic and hypochromic Low HCT Low Hgb Low iron Low ferritin Low hepcidin
Plummer-Vinson syndrome
microcytic hypochromic anemia
esophageal webs
atrophic glossitis
aplastic anemia
syndrome of chronic primary hematopoietic failure and subsequent pancytopenia
causes include aquired, chemical agents, physical agents and inherited
typical anemia sx
reticulocytopenia; NO splenomegaly
pure red cell aplasia
primary marrow disorder with only RBC precurors affected
causes include thymoma, autoimmune or parvovirus B19
PTT measures which clotting pathway?
Intrinsic
XII, XI, IX, VIII
PT meaures which clotting pathway?
Extrinsic
VII
Henoch-Schonlein purpura
systemic immune disorder characterized by purpuric rash, colicky abdominal pain, polyarthralgia, and acute glomerulonephritis
due to deposition of immune complexes
Hereditary hemorrhagic telangiectasia
AD disorder caused by mutations of genes that modulate TFG-B signaling
dilated, tortuous blodd vessels
bleeding common under mucous membranes
perivascular amyloidosis
amyloid light chain amyloidosis
mucocutaneous petechiae
chronic immune thrombocytopenic purpura
caused by autoantibody (IgG) destruction of platelets
can occur secondarily to SLE, HIV or B-cell neoplasms
tx: splenectomy
micro shows megathrombocytes
sx include petechiae, ecchymosis, mucosal bleeding, and hemorrhages
NO splenomegaly or lymphadenopathy
PT and PTT are normal
acute immune thrombocytopenic purpura
similar to chronic but mainly a disease of childhood
sx appear 1-2 weeks after a viral illness
resolves spontaneously
drug induced thrombocytopenia
typically caused by quinine, quinidine, and vancomycin
heparin-induced thrombocytopenia
causes severe life threatening venous and arterial thromboses
HIV-associated thrombocytopenia
HIV can infect megakaryocytes since they contain CD4 and CKCR4 receptor and coreceptor
infected megakaryocytes are prone to apoptosis and opsonization by immune complexes or splenic destruction
thrombotic thrombocytopenic purpura
deficiency in plasma enzyme ADAMTS13
causes thrombotic microangiopathies
widespread organ dysfunction
hemolytic-uremic syndrome
triggered by E. coli Shiga-like toxin which alters endothelial function and platelete aggregation causing thrombotic microangiopathies
widespread organ dysfunction
Bernard-Soulier syndrome
deficiency in endothelial platelet membrane complex Ib-IX (vWF receptor)
generally a pediatric disease with giant platelets in peripheral blood
severe bleeding tendency
Glanzmann thrombasthenia
deficiency in glycoprotein IIb-IIIa which aids in binding platelets to fibrinogen
mild to severe bleeding tendency
Hemophilia A
deficiency in factor VIII, which normally binds to vWF once in circulation
prolonged PTT with normal PT
easy bruising, massive hemorrhage after trauma, and spontaneous hemorrhage (hemarthroses)
tx: factor VIII infusions
von Willebrand disease
deficiency in vWF
only types 1 and 3 are clinically detected by prolonged PTT
type 2 is most common
Hemophilia B
factor IX deficiency
clinically indistinguishable from Hem A
prolonged PTT with normal PT
tx: factor IX infusions
Disseminated intravascular coaguation (DIC)
acute, subacute or chronic thrombohemorrhagic disorder characterized by excessive activation of coagulation and foration of thrombi in microvasulature
not a primary disease –complication of a variety of disorders
sx include microangiopathic hemolytic anemia, dyspnea, cyanosis, respiratory failure, subacute renal failure, circulatory failure/shock
tx: treat the underlying cause
