Notes in 39) Paroxysmal Nocturnal Hemoglobinuria

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Published	06/12/2025	1) In the classic case scenario, a 30-year-old man presents with dark-colored morning urine, abdominal pain, and hepatic vein thrombosis. Which rare a…
Published	06/12/2025	2) What is the fundamental genetic defect in PNH?
Published	06/12/2025	3) How does the PIGA mutation lead to red blood cell destruction by complement?
Published	06/12/2025	4) Which two GPI-anchored proteins are most important in protecting RBCs from complement in PNH?
Published	06/12/2025	5) Why is PNH considered the only hemolytic anemia due to an acquired intrinsic RBC defect?
Published	06/12/2025	6) Clinically, why is PNH known for 'dark urine in the morning'?
Published	06/12/2025	7) How does the term 'paroxysmal' in PNH relate to its actual clinical presentation?
Published	06/12/2025	8) What role do CD55 (DAF) and CD59 (MIRL) normally play in RBC protection?
Published	06/12/2025	9) Why is a negative direct Coombs test (antiglobulin test) a hallmark in PNH?
Published	06/12/2025	10) PNH can involve the destruction of RBCs, WBCs, and platelets. What term describes this simultaneous reduction of all cell lines?
Published	06/12/2025	11) What major vascular complication is the leading cause of mortality in PNH?
Published	06/12/2025	12) Why does PNH have a propensity for venous thromboses, such as Budd-Chiari syndrome?
Published	06/12/2025	13) How can free hemoglobin (released by intravascular hemolysis) reduce nitric oxide (NO)?
Published	06/12/2025	14) Which symptom in PNH can be linked to nitric oxide depletion besides thrombosis?
Published	06/12/2025	15) Name three major clinical features commonly emphasized in PNH.
Published	06/12/2025	16) Which form of anemia is typically Coombs-negative and involves RBC membrane skeleton defects, making it a key differential for PNH?
Published	06/12/2025	17) In an exam stem, you see hemolytic anemia, pancytopenia, and negative Coombs test. Which key diagnosis must you suspect?
Published	06/12/2025	18) Why might patients with PNH eventually develop iron deficiency anemia?
Published	06/12/2025	19) Why can PNH cause episodes of abdominal pain?
Published	06/12/2025	20) Which older test historically diagnosed PNH by demonstrating RBC lysis in acidified serum?
Published	06/12/2025	21) In modern practice, what is the gold-standard test to confirm PNH?
Published	06/12/2025	22) How does FLAER (fluorescent aerolysin) help diagnose PNH on flow cytometry?
Published	06/12/2025	23) What is the significance of detecting subpopulations of RBCs or WBCs lacking CD55/CD59 in flow cytometry?
Published	06/12/2025	24) If a patient with presumed hemoglobinuria is found to have RBCs on urine microscopy, what does that suggest instead of PNH?
Published	06/12/2025	25) Which abnormal marrow finding can PNH share with aplastic anemia?
Published	06/12/2025	26) Why can PNH overlap with aplastic anemia (AA)?
Published	06/12/2025	27) What percentage of aplastic anemia patients may harbor a small PNH clone?
Published	06/12/2025	28) Name a key difference between PNH and autoimmune hemolytic anemia (AIHA).
Published	06/12/2025	29) What RBC findings are typically seen in warm autoimmune hemolysis but not in PNH?
Published	06/12/2025	30) Why is intravascular hemolysis particularly high in PNH compared to many other anemias?
Published	06/12/2025	31) A 28-year-old man of Mediterranean descent develops dark urine after sulfa drugs. Why is G6PD deficiency more likely than PNH here?
Published	06/12/2025	32) Name one test that is historical for G6PD deficiency but might appear on exams.
Published	06/12/2025	33) What major feature differentiates PNH from microangiopathic hemolytic anemias (like TTP/HUS) on a blood smear?
Published	06/12/2025	34) Which vascular bed is commonly involved in PNH that leads to Budd-Chiari syndrome?
Published	06/12/2025	35) What is Budd-Chiari syndrome?
Published	06/12/2025	36) A patient has acute onset hepatic vein thrombosis and negative Coombs test. Why should PNH be a top differential?
Published	06/12/2025	37) How can PNH lead to cerebral venous sinus thrombosis?
Published	06/12/2025	38) Which symptom might a male PNH patient experience due to nitric oxide depletion?
Published	06/12/2025	39) Why might PNH cause dysphagia?
Published	06/12/2025	40) What lab findings indicate intravascular hemolysis in PNH (or other causes)?
Published	06/12/2025	41) Why do PNH patients sometimes have macrocytosis on CBC?
Published	06/12/2025	42) What does a negative Coombs test but positive complement-mediated RBC destruction suggest about the pathophysiology?
Published	06/12/2025	43) What is the historical 'sucrose hemolysis test' for PNH?
Published	06/12/2025	44) In PNH, how does RBC destruction differ from hereditary spherocytosis (HS)?
Published	06/12/2025	45) In PNH, which direct RBC membrane-destroying complex is formed unchecked?
Published	06/12/2025	46) List one reason RBC fragments (schistocytes) are typically not seen in PNH.
Published	06/12/2025	47) Is there a specific morphological RBC finding on smear that confirms PNH?
Published	06/12/2025	48) What is the classic RBC test to differentiate autoimmune hemolysis from PNH?
Published	06/12/2025	49) How do clinicians confirm that RBC destruction in PNH is specifically complement-driven?
Published	06/12/2025	50) Name the key triad that helps differentiate PNH from many other anemias:
Published	06/12/2025	51) What supportive measures are often provided to PNH patients with ongoing hemolysis?
Published	06/12/2025	52) What breakthrough therapy drastically changed the prognosis of PNH?
Published	06/12/2025	53) How does eculizumab prevent hemolysis?
Published	06/12/2025	54) Which bacterium poses a higher risk of infection in PNH patients on eculizumab?
Published	06/12/2025	55) What vaccination is recommended before starting eculizumab therapy?
Published	06/12/2025	56) Name a more recent, long-acting C5 inhibitor used in PNH.
Published	06/12/2025	57) What is the only curative treatment for PNH (though high risk)?
Published	06/12/2025	58) Why might an older reference mention 'acid hemolysis test' for diagnosing PNH?
Published	06/12/2025	59) How does nitric oxide scavenging by free hemoglobin contribute to the smooth muscle issues seen in PNH?
Published	06/12/2025	60) In a PNH patient, where might you see hemosiderin deposits due to chronic hemoglobinuria?
Published	06/12/2025	61) How can PNH overlap or evolve into myelodysplastic syndrome or acute leukemia?
Published	06/12/2025	62) Does PNH classically present with massive splenomegaly like some hemolytic anemias?
Published	06/12/2025	63) Why might the RBC count in PNH sometimes appear macrocytic without B12/folate deficiency?
Published	06/12/2025	64) Which RBC lab test is characteristically negative in PNH but might be positive in cold AIHA (due to IgM)?
Published	06/12/2025	65) Describe the typical RBC destruction pattern in G6PD deficiency vs. PNH.
Published	06/12/2025	66) If you suspect PNH in an exam question, what distinguishing lab test result should you look for besides negative Coombs?
Published	06/12/2025	67) Which RBC component is spontaneously produced at low levels, leading to mild, continuous complement activation that normally gets regulated by CD5…
Published	06/12/2025	68) In a Step 1 vignette, what combination of lab findings strongly suggests PNH?
Published	06/12/2025	69) What might you see in bone marrow biopsy of a PNH patient who also shows signs of aplastic anemia?
Published	06/12/2025	70) Why is the RBC lifespan shortened in PNH?
Published	06/12/2025	71) In PNH, how does complement activation on platelets contribute to morbidity?
Published	06/12/2025	72) If a patient has repeated venous thromboses in unusual sites, especially hepatic or portal veins, what hematological disorder should you rule out?
Published	06/12/2025	73) Which test has largely replaced the sucrose hemolysis test for diagnosing PNH?
Published	06/12/2025	74) How does iron loss occur chronically in PNH?
Published	06/12/2025	75) How does eculizumab improve survival rates in PNH patients?
Published	06/12/2025	76) Why might RBC transfusions still be necessary in PNH despite eculizumab therapy?
Published	06/12/2025	77) What is the major limitation or caution with eculizumab therapy?
Published	06/12/2025	78) When evaluating an unknown hemolytic anemia, why is distinguishing between intravascular vs. extravascular hemolysis crucial?
Published	06/12/2025	79) If a PNH patient has low platelets and mild bleeding, which aspect of the disease might explain it?
Published	06/12/2025	80) Name one reason PNH can present with recurrent infections.
Published	06/12/2025	81) How do you differentiate hemoglobinuria (PNH) from hematuria on a dipstick test?
Published	06/12/2025	82) Why might you see elevated reticulocyte count in PNH?
Published	06/12/2025	83) Which antibiotic class is known to precipitate hemolysis in G6PD deficiency but does not typically trigger PNH episodes?
Published	06/12/2025	84) List two RBC morphological findings that might be seen in G6PD deficiency but not PNH.
Published	06/12/2025	85) A negative Coombs test with spherocytes on smear suggests what disorder, not PNH?
Published	06/12/2025	86) A 35-year-old with RBC casts in urine vs. one with RBC-free 'cola-colored' urine: which is more consistent with PNH?
Published	06/12/2025	87) Why might RBC fragmentation (schistocytes) be absent in PNH yet present in TTP/HUS/DIC?
Published	06/12/2025	88) Patients with PNH might have mild splenomegaly, but what major RBC disorder is more famously associated with marked splenomegaly?
Published	06/12/2025	89) How does iron deficiency from PNH often manifest on labs?
Published	06/12/2025	90) In the pathophysiology of PNH, what is the significance of the 'alternative pathway' of complement?
Published	06/12/2025	91) What might be an exam clue differentiating PNH from paroxysmal cold hemoglobinuria (PCH)?
Published	06/12/2025	92) Why do patients with PNH sometimes have mild jaundice or elevated unconjugated bilirubin?
Published	06/12/2025	93) How can you explain that not all RBCs are destroyed in PNH but only a certain percentage at a time?
Published	06/12/2025	94) When might a bone marrow transplant be strongly considered in PNH?
Published	06/12/2025	95) What specific RBC membrane defect do hereditary spherocytosis patients have?
Published	06/12/2025	96) A 40-year-old with past aplastic anemia develops new-onset hemoglobinuria. Why suspect PNH?
Published	06/12/2025	97) Besides RBC destruction, why does intravascular hemolysis lead to high LDH?
Published	06/12/2025	98) What prophylaxis is sometimes considered for PNH patients at high risk of thrombosis?
Published	06/12/2025	99) Why doesn't PNH typically present in infancy like hereditary hemolytic disorders?
Published	06/12/2025	100) If a question states 'hemolysis with partial RBC membrane oxidation' or 'oxidative stress,' which condition do you suspect over PNH?
Published	06/12/2025	101) Which RBC destruction test has replaced older assays like Ham’s test due to better sensitivity/specificity?
Published	06/12/2025	102) In which type of anemia are RBCs destroyed primarily in the spleen?
Published	06/12/2025	103) If reticulocyte count is low in a PNH patient, what does that suggest?
Published	06/12/2025	104) What are the main treatments for severe aplastic anemia if PNH is not the predominant issue?
Published	06/12/2025	105) If a PNH question focuses on 'flow cytometry with cells missing CD55/CD59,' how should you answer the diagnosis?
Published	06/12/2025	106) During PNH hemolysis, what by-product might discolor the urine aside from hemoglobin?
Published	06/12/2025	107) Why does eculizumab not completely eliminate all hemolysis in some PNH patients?
Published	06/12/2025	108) What emerging treatment blocks C3 to address extravascular hemolysis in PNH?
Published	06/12/2025	109) Which two anemias might show RBCs with 'bite cells'?
Published	06/12/2025	110) In the pathophysiology analogy, RBCs lacking GPI-anchored proteins are described as what?
Published	06/12/2025	111) Why do many PNH patients require iron supplementation over time?
Published	06/12/2025	112) What triggers RBC destruction in cold autoimmune hemolysis but not in PNH?
Published	06/12/2025	113) Which clinical symptom might a USMLE question highlight to suggest Budd-Chiari syndrome?
Published	06/12/2025	114) A 32-year-old with negative Coombs test, elevated D-dimer, and hepatic vein thrombosis is most likely suffering from?
Published	06/12/2025	115) Why might a PNH patient have mild jaundice yet normal stool color?
Published	06/12/2025	116) How might PNH contribute to an increased reticulocyte index?
Published	06/12/2025	117) Which RBC index might be elevated if hemolysis is brisk in PNH?
Published	06/12/2025	118) Why is eculizumab not curative but primarily palliative in PNH?
Published	06/12/2025	119) How might PNH eventually transform into acute leukemia?
Published	06/12/2025	120) Which two conditions could a USMLE question describe evolving within the same patient with a clonal hematopoietic disorder?
Published	06/12/2025	121) Which test might read 'positive for blood' on dipstick but show no RBCs in microscopic exam in PNH?
Published	06/12/2025	122) What is the main effect of absent GPI anchors on leukocytes in PNH?
Published	06/12/2025	123) In PNH, does RBC destruction primarily happen in spleen or in circulation?
Published	06/12/2025	124) Name one cause of extravascular hemolysis that is Coombs-positive.
Published	06/12/2025	125) Which RBC index might remain low if the marrow is also failing in PNH?
Published	06/12/2025	126) How does an episode of hemoglobinuria typically appear in the morning for a PNH patient?
Published	06/12/2025	127) What mechanism explains the association of RBC lysis with sleep in PNH?
Published	06/12/2025	128) In PNH, what is the direct result of uncontrolled complement on RBC membranes?
Published	06/12/2025	129) How does RBC destruction in PNH differ from RBC destruction in warm AIHA?
Published	06/12/2025	130) A patient with PNH might have partial RBC protection if some RBCs...
Published	06/12/2025	131) Which major clotting risk factor do PNH platelets lack?
Published	06/12/2025	132) If an exam question describes abdominal pain, esophageal spasm, and erectile dysfunction along with hemolysis, which unifying factor is implicate…
Published	06/12/2025	133) Which age group is PNH most commonly diagnosed in?
Published	06/12/2025	134) Does PNH generally cause extravascular hemolysis or intravascular hemolysis?
Published	06/12/2025	135) How does complement overactivity in PNH lead to platelet consumption?
Published	06/12/2025	136) Name a condition that can mimic PNH by causing intermittent hemoglobinuria but is Coombs-positive.
Published	06/12/2025	137) Why might anemia in PNH occasionally appear macrocytic?
Published	06/12/2025	138) What might you suspect if a PNH patient has persistent anemia despite eculizumab with evidence of extravascular RBC breakdown?
Published	06/12/2025	139) How can RBC transfusions temporarily relieve symptoms in PNH?
Published	06/12/2025	140) If a USMLE question highlights a patient with hepatic vein thrombosis and negative Coombs test, what is the best next diagnostic step?
Published	06/12/2025	141) Why might PNH sometimes present with mild confusion or headache?
Published	06/12/2025	142) If no RBCs are seen in the urine of a 'cola-colored urine' sample, what does that strongly suggest?
Published	06/12/2025	143) In an exam question, why is RBC transfusion alone not sufficient long-term therapy for PNH?
Published	06/12/2025	144) What is the main reason eculizumab greatly improves quality of life in PNH patients?
Published	06/12/2025	145) Why does eculizumab therapy in PNH reduce the risk of hepatic vein thrombosis?
Published	06/12/2025	146) Which form of hemolysis involves RBCs being phagocytosed in the spleen—PNH or AIHA?
Published	06/12/2025	147) If a PNH patient develops fullness in the abdomen and mild splenomegaly, what might you consider?
Published	06/12/2025	148) Which lab value commonly reflects RBC turnover in PNH?
Published	06/12/2025	149) Is the direct bilirubin typically elevated in PNH?
Published	06/12/2025	150) An exam question states: 'A monoclonal antibody therapy that blocks complement component C5 is given.' Name the drug and the condition treated.
Published	06/12/2025	151) What precaution is mandatory before initiating eculizumab treatment?
Published	06/12/2025	152) Which newer therapy might appear on exams that targets C3 to treat PNH?
Published	06/12/2025	153) In a patient with high risk PNH (large clone, history of thromboses), what definitive treatment may be offered if a donor is available?
Published	06/12/2025	154) Why might an exam vignette mention 'evidence of intravascular hemolysis and a 'PNH clone' on flow cytometry' after a patient recovers from aplast…
Published	06/12/2025	155) What is the most direct pathophysiologic reason PNH RBCs succumb to complement?
Published	06/12/2025	156) Name the typical triad that an exam question might provide to point you toward PNH.
Published	06/12/2025	157) How might eculizumab improve dysphagia or abdominal pain in PNH?
Published	06/12/2025	158) Why does the word 'nocturnal' in PNH remain despite recognition that hemolysis isn’t strictly nocturnal?
Published	06/12/2025	159) Which RBC test might still show RBC lysis in older references if RBCs are exposed to low pH serum?
Published	06/12/2025	160) Summarize the essential mechanism behind PNH in one concise sentence.
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