Identify non-immune extrinsic causes of hemolysis โ€” microangiopathic, mechanical โ€” for ASCP hematology MCQs.

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Chapter 14 โ€” EXTRINSIC DEFECTS LEADING TO INCREASED ERYTHROCYTE DESTRUCTION: NONIMMUNE CAUSES

ASCP Board Exam ยท Lab-Focused Study Guide
Microangiopathic Hemolytic Anemia (TTP ยท HUS ยท HELLP ยท DIC) ยท Macroangiopathic Hemolysis ยท Malaria (5 Plasmodium Species, Thick & Thin Films) ยท Babesiosis ยท Clostridial Sepsis ยท Bartonellosis ยท Drugs, Chemicals, Venoms & Burns ยท Practice Questions

1 ยท Priority Table & Quick Foundation

Topic Priority Why It’s Tested
Microangiopathic hemolytic anemia (MAHA): schistocytes + thrombocytopenia HIGH Rodak review Q1โ€“Q2; the core pattern of the chapter
TTP: ADAMTS-13 deficiency, ULVWF, normal PT/PTT, plasma exchange HIGH Mechanism and treatment; Rodak Q3 and Q11 case
TTP vs HUS vs HELLP vs DIC (platelets, renal, liver enzymes, coagulation tests) HIGH Differentiation โ€” PT/PTT separates DIC (Rodak Q4)
Malaria: 5 species morphology, erythrocytic cycle length, age of RBC invaded HIGH Film identification; Rodak Q6โ€“Q8 and case study
Thick vs thin films: preparation, staining, purpose, number of fields HIGH Specimen and procedure questions
Babesiosis vs P. falciparum (tetrads, no pigment, no gametocytes) HIGH Classic look-alike on the film; Rodak Q9
Traumatic cardiac hemolysis vs exercise-induced hemoglobinuria MEDIUM Macroangiopathic causes โ€” normal platelets (Rodak Q5)
Mechanisms of anemia in P. falciparum; PfEMP1, cytoadherence, cerebral malaria MEDIUM Pathophysiology (Rodak Q7)
Clostridial sepsis: ฮฑ-toxin, spherocytes, massive intravascular hemolysis MEDIUM Film + history matching
Extensive burns: schistocytes, spherocytes, microspherocytes within 24 h MEDIUM Rodak Q10
Protective polymorphisms (Duffy-negative, Hb S, Hb C, Hb E, thalassemia, G6PD) MEDIUM Geneticsโ€“infection link
Bartonellosis (Oroya fever), venoms, drugs/chemicals (dapsone, naphthalene) LOW Less common; recognition only
Rapid antigen test (BinaxNOW: HRP-II, aldolase), PCR, fluorescent dyes LOW Other diagnostic methods
๐ŸŽฏ KEY POINT โ€” Where to spend your time

Focus: the MAHA pattern (schistocytes, โ†“ platelets), what separates TTP, HUS, HELLP and DIC, the ADAMTS-13 mechanism, the malaria species table (RBC size, stippling, forms seen, cycle length), thick vs thin film technique, and Babesia vs falciparum. Skim: epidemiology numbers, Babesia species by U.S. state, bartonellosis history, venom species names.

Quick Foundation โ€” from zero

  • In extrinsic hemolytic anemias the RBC is normal โ€” something outside the cell damages it. Transfuse normal cells into these patients and they get destroyed too.
  • This chapter covers the nonimmune causes (no antibody). Immune hemolysis is the next chapter.
  • The common thread is physical or mechanical injury: cells get sliced by clots in tiny vessels (microangiopathic), battered by heart valves or foot strikes (macroangiopathic), invaded by parasites (malaria, Babesia), attacked by bacterial toxins (Clostridium), or damaged by drugs, venoms and heat.
  • The peripheral blood film is the key clue: schistocytes (fragments), spherocytes or intracellular organisms.
  • In MAHA, platelets are used up forming the microthrombi, so thrombocytopenia accompanies the schistocytes. In macroangiopathic hemolysis, platelets stay normal.
๐Ÿ’ก Analogy

Think of RBCs as cyclists on a road. In MAHA, wires (fibrin/platelet strands) are strung across narrow side streets โ€” cyclists get sliced in half (schistocytes), and the wire material (platelets) is used up. In macroangiopathic hemolysis, the road itself is dangerous โ€” a broken bridge (faulty heart valve) or pounding potholes (foot strikes in runners). In malaria, a hijacker climbs aboard and eats the cyclist from inside. Clostridium is acid thrown on the road โ€” it dissolves the tires (membrane lipids).

๐Ÿฅ Why this matters clinically

Several of these are emergencies where the laboratory makes the call. Seeing schistocytes with severe thrombocytopenia and normal PT/PTT should trigger urgent reporting โ€” untreated TTP is often fatal, and plasma exchange saves 80โ€“90%. Finding P. falciparum or P. knowlesi means treatment must start without delay. Platelet transfusion is avoided in TTP*.

*Platelet transfusion caution in TTP is standard clinical teaching, not stated in Rodak Ch. 25.

Concept Plain-English Explanation
Extrinsic hemolytic anemia Normal RBCs destroyed by a cause outside the cell
Schistocyte RBC fragment formed when the cell is sheared (helmet cell is one type)
Microangiopathic (MAHA) Shearing in small vessels partly blocked by microthrombi or damaged endothelium
Thrombotic microangiopathy Another name for MAHA โ€” stresses the platelet-rich microthrombi
Macroangiopathic Injury from the heart or large vessels (valves) or external impact
ADAMTS-13 Enzyme that trims ultra-large VWF multimers into smaller, less sticky pieces
Parasitemia Percentage of RBCs containing parasites
Hypnozoite Dormant liver stage of P. vivax and P. ovale that causes relapse

2 ยท Core Content Tables

2.1 Extrinsic Nonimmune Causes of Hemolytic Anemia (Rodak Box 25-1)

Group Conditions Key Film Clue
Microangiopathic hemolytic anemia TTP ยท HUS ยท HELLP syndrome ยท DIC Schistocytes, helmet cells + โ†“ platelets
Macroangiopathic hemolytic anemia Traumatic cardiac hemolytic anemia ยท exercise-induced hemoglobinuria Schistocytes (cardiac), normal platelets
Infection Malaria ยท babesiosis ยท clostridial sepsis ยท bartonellosis Intracellular organisms; spherocytes in clostridial sepsis
RBC injury โ€” other Chemicals ยท drugs ยท venoms ยท extensive burns Heinz bodies (oxidants); schistocytes/microspherocytes (burns)

2.2 Microangiopathic Hemolytic Anemia โ€” General Features

Feature Details
Mechanism RBCs pass rapidly through turbulent areas of small vessels partly blocked by microthrombi or damaged endothelium โ†’ membranes sheared intravascularly
Fragments Membranes reseal with little Hb loss, but fragments (schistocytes) are distorted and rigid โ†’ cleared by the spleen (extravascular)
Severe cases Fragmentation so severe that intravascular hemolysis also occurs: hemoglobinemia, hemoglobinuria, markedly โ†“ haptoglobin
Hemolysis labs โ†“ Hb, โ†‘ retics, โ†‘ indirect bilirubin, โ†‘ LDH, โ†“ haptoglobin, โ†‘ urine urobilinogen
Film Schistocytes (characteristic), helmet cells, occasional microspherocytes; polychromasia and nRBCs depending on severity
Thrombocytopenia Platelets consumed in the microthrombi โ†’ also called thrombotic microangiopathies
Main examples TTP, HUS, HELLP syndrome, DIC

2.3 Typical Laboratory Findings in TTP and HUS (Rodak Box 25-2)

Category Findings
Hematologic โ†“ Hemoglobin ยท โ†“ platelets ยท โ†‘ reticulocyte count
Peripheral blood film Schistocytes ยท polychromasia ยท nucleated RBCs (severe cases)
Biochemical Markedly โ†‘ LDH (ischemia + hemolysis; more in TTP) ยท โ†‘ total and indirect bilirubin ยท โ†“ haptoglobin ยท hemoglobinemia ยท hemoglobinuria ยท proteinuria, hematuria, casts (renal failure; more in HUS)

2.4 Thrombotic Thrombocytopenic Purpura (TTP)

Feature Details
Definition Rare, life-threatening: abrupt MAHA, severe thrombocytopenia, markedly โ†‘ LDH; neurologic dysfunction, fever and renal failure may occur but are not consistent
Who Most common in adults in their fourth decade; more females than males; can occur at any age
Cause Deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) โ€” the VWF-cleaving protease
Normal ADAMTS-13 role Cleaves ultra-large VWF multimers (ULVWF) at the A2 domain into smaller, less active pieces. Cleavage sites and the GP Ibฮฑ binding site (A1 domain) are hidden until ULVWF is unrolled: (1) release from endothelial cells, (2) high shear in small vessels, (3) binding to subendothelial collagen after injury
When deficient ULVWF stays on endothelial cells, unrolls under shear โ†’ platelets bind A1 โ†’ plateletโ€“VWF microthrombi block small vessels โ†’ severe thrombocytopenia, ischemia (brain, kidney), MAHA โ†’ striking โ†‘ LDH
Idiopathic TTP No precipitating event; autoantibodies (usually IgG; can be IgM or IgA) inhibit ADAMTS-13 โ†’ severe deficiency
Secondary TTP Infections, pregnancy, surgery, trauma, inflammation, disseminated malignancy (may โ†“ synthesis); HSCT, autoimmune disorders, HIV, drugs (quinine, ticlopidine, trimethoprim) โ†’ inhibitory reaction. Deficiency less severe
Inherited TTP Upshaw-Schรผlman syndrome: ADAMTS13 gene mutations (>75 known); homozygous or compound heterozygous; infancy/childhood with recurrences, or adulthood when stressed (pregnancy, severe infection)

2.5 TTP โ€” Laboratory Findings

Feature Details
CBC Hb 8โ€“10 g/dL ยท platelets 10โ€“30 ร— 10โน/L ยท WBC often โ†‘, immature granulocytes may appear
Film Schistocytes; polychromasia and nRBCs once marrow responds
Marrow Erythroid hyperplasia; normal number of megakaryocytes
Chemistry LDH markedly โ†‘; haptoglobin โ†“; indirect bilirubin rise delayed several days after acute onset
Urine Hemoglobinuria (extensive intravascular hemolysis); variable protein, RBCs, casts
Coagulation PT and PTT usually within reference interval โ€” separates TTP from DIC
ADAMTS-13 Idiopathic and inherited: activity <5โ€“10% of normal. Secondary: deficiency less severe. Autoantibodies detected in idiopathic, absent in inherited

2.6 TTP โ€” Treatment

Feature Details
Idiopathic Plasma exchange โ€” 80โ€“90% respond (removes autoantibody, supplies ADAMTS-13 from donor plasma). Must be started quickly to avoid a fatal outcome. Corticosteroids suppress autoimmunity
Relapse About one third of responders relapse; rituximab (anti-CD20) helps some
Secondary Generally poor response to plasma exchange; poor prognosis except TTP related to autoimmune disease, pregnancy or ticlopidine
Inherited Plasma exchange not required โ€” infuse fresh frozen plasma to supply ADAMTS-13

2.7 Hemolytic Uremic Syndrome (HUS)

Feature Details
Definition MAHA + thrombocytopenia + acute renal failure from damage to glomerular endothelial cells
Typical (stx-HUS) ~90% of HUS. Shiga toxinโ€“producing E. coli (STEC), e.g., O157:H7; also toxin-producing Shigella. Mostly young children. Acute gastroenteritis, often bloody diarrhea โ†’ 5โ€“13 days later oliguria and renal damage; ~ยผ have neurologic signs
Shiga toxin mechanism Stx-1 and Stx-2 (verotoxins) absorbed from the gut โ†’ bind Gb3 (CD77) receptors on endothelial cells (glomerulus, brain) โ†’ inhibit protein synthesis โ†’ endothelial injury and apoptosis; cytokines make endothelium prothrombotic (tissue factor, adhesion molecules, โ†‘ ULVWF) โ†’ plateletโ€“fibrin thrombi โ†’ acute renal failure
Stx-HUS treatment No specific therapy; supportive (hydration, dialysis, transfusion). Resolves in 1โ€“3 weeks; favorable prognosis
Atypical (aHUS) ~10%. Uncontrolled activation of the alternative complement pathway. 50โ€“70% inherited mutations: inactivating in factor H, factor I, membrane cofactor protein, thrombomodulin; activating in factor B and C3. Acquired form: autoantibodies to factor H (5โ€“10%). Triggers: HSCT, pregnancy, infection, inflammation, surgery, trauma
aHUS treatment Plasma exchange/infusion of limited value; eculizumab (anti-C5) improves platelets and renal function โ€” may become therapy of choice
Labs vs TTP Platelets only mildly to moderately โ†“; renal failure evident: โ†‘ creatinine, proteinuria, hematuria, hyaline, granular and RBC casts
Diagnostic challenge aHUS vs TTP difficult; ADAMTS-13 assays lack sensitivity/specificity and aren’t widely available; complement gene testing too slow for initial decisions

2.8 HELLP Syndrome

Feature Details
Name Hemolysis, Elevated Liver enzymes, Low Platelet count
Frequency <1% of all pregnancies; 10โ€“20% of pregnancies with severe preeclampsia; usually third trimester
Pathogenesis Abnormal placental vasculature โ†’ poor perfusion, hypoxia โ†’ antiangiogenic proteins block placental growth factors (VEGF) โ†’ maternal endothelial dysfunction โ†’ platelet activation, fibrin deposition, especially in the liver
Labs Anemia, hemolysis, schistocytes ยท platelets <100 ร— 10โน/L (<50 = worse prognosis) ยท โ†‘ LDH (liver necrosis + hemolysis) ยท markedly โ†‘ AST
Key differentiator PT and PTT within reference interval โ€” distinguishes HELLP from DIC
Treatment / outcome Deliver the fetus and placenta ASAP; control seizures, hypertension, fluids. Mortality 3โ€“5% (mother), 9โ€“24% (fetus)

2.9 Disseminated Intravascular Coagulation (DIC)

Feature Details
Definition Widespread activation of hemostasis โ†’ fibrin thrombi throughout the microvasculature โ†’ organ damage + bleeding (consumed platelets and factors; secondary fibrinolysis)
Causes Metastatic cancer, acute leukemias, infections, obstetric complications, crush/brain injury, acute hemolytic transfusion reactions, extensive burns, snake/spider envenomation, chronic inflammation
Film Thrombocytopenia is consistent; schistocytes in only about half of patients
Key labs Prolonged PT and PTT, โ†“ fibrinogen, โ†‘ D-dimer โ€” distinguishes DIC from other MAHAs (covered in the hemostasis chapters)

2.10 Comparing the Microangiopathies

Feature TTP HUS (typical) HELLP DIC
Typical patient Adult, 4th decade, female Young child after bloody diarrhea Pregnant, 3rd trimester, preeclampsia Underlying disease (sepsis, cancer, obstetric)
Platelets Severely โ†“ (10โ€“30) Mildโ€“moderate โ†“ <100 ร— 10โน/L โ†“ (variable)
Schistocytes Present Present Present ~Half of cases
LDH Markedly โ†‘ โ†‘ โ†‘ โ†‘*
Renal findings Variable Acute renal failure, โ†‘ creatinine, casts โ€” Possible
Liver enzymes (AST) โ€” โ€” Markedly โ†‘ Possible*
PT / PTT Normal Normal Normal Prolonged
Fibrinogen / D-dimer Normal* Normal* Normal* โ†“ / โ†‘
Key mechanism ADAMTS-13 deficiency โ†’ plateletโ€“VWF thrombi Shiga toxin (typical) or complement (atypical) Placental endothelial dysfunction Systemic coagulation activation
Treatment Plasma exchange, steroids, rituximab Supportive; eculizumab (aHUS) Delivery Treat the cause

*Cells marked with an asterisk are general hematology expectations not stated explicitly in Rodak Ch. 25.

2.11 Traumatic Cardiac Hemolytic Anemia (Macroangiopathic)

Feature Details
Cause Prosthetic heart valves โ€” turbulent flow through and around the device; severe hemolysis usually from paravalvular leaks. Also native valve disease before surgery
Severity Usually mild; marrow compensates, anemia uncommon. Severe: pallor, fatigue, even heart failure
Film Schistocytes characteristic
Labs โ†‘ Retics ยท platelets within reference interval ยท โ†‘ LDH ยท โ†‘ indirect bilirubin ยท โ†‘ plasma Hb ยท โ†“ haptoglobin ยท hemoglobinuria (severe)
Chronic hemoglobinuria Hemosiderinuria and โ†“ serum ferritin (urinary iron loss) โ†’ may become microcytic (iron deficiency); otherwise normocytic
Treatment Surgical repair/replacement if transfusion-dependent; iron supplements for hemoglobinuria; folic acid for increased erythropoiesis

2.12 Exercise-Induced Hemoglobinuria (March Hemoglobinuria*)

Feature Details
Who Long-distance runners; to a lesser extent intensive cycling and swimming; strenuous hand drumming. Frank hemoglobinuria is rare
Proposed causes Mechanical trauma from repeated forceful impact of feet/hands on hard surfaces; increased RBC susceptibility to oxidative stress; exercise-induced changes in membrane skeletal proteins
Labs โ†“ Haptoglobin ยท โ†‘ free plasma Hb ยท hemoglobinuria after strenuous exercise ยท slight โ†‘ MCV and retics
Film Schistocytes not present except in rare cases
Anemia Usually none unless hemoglobinuria is severe and recurrent
Diagnosis Diagnosis of exclusion โ€” other causes of hemolysis and hemoglobinuria must be ruled out
Management No treatment; padding on the feet, softer running surfaces, or stopping the activity if severe

*’March hemoglobinuria’ is the classic alternate name from general references.

2.13 Malaria โ€” Epidemiology & Species

Feature Details
Organism Protozoa of genus Plasmodium: P. falciparum and P. vivax (most human infections), P. ovale, P. malariae, and P. knowlesi (macaque parasite)
P. knowlesi Easily misdiagnosed as P. malariae by microscopy; PCR showed many Malaysian ‘P. malariae’ cases were P. knowlesi; widespread in Malaysia and Southeast Asia
Burden (2012) ~3.4 billion people at risk; 207 million cases; 627,000 deaths, mostly children <5 years. Deaths: Africa 90%, Southeast Asia 7%, Eastern Mediterranean 3%
United States 1925 cases in 2011, nearly all travel-related; P. falciparum and P. vivax most common
Other transmission Congenital, blood transfusion, organ transplantation, shared needles

2.14 Plasmodium Life Cycle

Feature Details
Vector Bite of an infected female Anopheles mosquito injects sporozoites from its salivary gland
Exoerythrocytic schizogony Sporozoites invade hepatocytes; after 5โ€“16 days liver cells rupture, releasing tens of thousands of merozoites
Erythrocytic schizogony Merozoite โ†’ ring form โ†’ mature trophozoite โ†’ immature schizont (chromatin dividing) โ†’ mature schizont (merozoites) โ†’ RBC ruptures โ†’ new RBCs infected
Fever pattern Cycles become synchronous โ†’ paroxysms of fever and chills at a frequency that depends on the species
Hypnozoites Dormant liver stages of P. vivax and P. ovale โ†’ relapse months or years later
Sexual stage Some merozoites form male and female gametocytes โ†’ ingested by mosquito โ†’ zygote โ†’ ookinete โ†’ oocyst โ†’ sporozoites migrate to salivary glands

2.15 Malaria โ€” Pathogenesis

Feature Details
Outcomes of a bite No infection ยท asymptomatic parasitemia ยท uncomplicated malaria (symptoms, no organ dysfunction) ยท severe malaria (major organ dysfunction)
Risk groups (endemic areas) Children <5 years and women in first pregnancy; travelers and low-transmission areas โ€” all ages
Severe malaria Mostly P. falciparum (P. vivax and P. knowlesi can too); hyperparasitemia >2โ€“5%; ARDS, metabolic acidosis, shock, renal/hepatic failure, hypoglycemia, severe anemia (Hb <5 g/dL), poor pregnancy outcome, cerebral malaria; fatality 10โ€“20% even with treatment
Causes of anemia (1) Lysis of infected RBCs during schizogony ยท (2) immune destruction of infected AND noninfected RBCs in the spleen (parasite proteins bind noninfected cells โ†’ Ig/complement โ†’ splenic removal; oxidative damage) ยท (3) inhibition of erythropoiesis and ineffective erythropoiesis (TNF-ฮฑ, IFN-ฮณ; IL-6 โ†’ โ†‘ hepcidin โ†’ โ†“ iron)
Hemozoin Toxic ‘malaria pigment’ from Hb metabolism; released at schizogony โ†’ inflammation and cytokine imbalance
P. falciparum cytoadherence Infected RBCs express PfEMP1 โ†’ bind CD36 (platelets, some endothelium) and other receptors โ†’ adhere in brain, heart, lung, liver, kidney, dermis, placenta โ†’ obstruction, โ†“ Oโ‚‚, escape splenic clearance
Cerebral malaria Complex of VWF (from stimulated endothelium), platelets and infected RBCs bound to platelet CD36; a PfEMP1 variant binds endothelial protein C receptor (EPCR) โ†’ blocks protein C activation โ†’ local hypercoagulability
Placental malaria Local inflammation โ†’ severe maternal anemia, low birth weight, premature delivery, fetal loss

2.16 RBC Age Preference & Protective Traits

Feature Details
Reticulocytes only P. vivax and P. ovale
Older RBCs only P. malariae
RBCs of all ages P. falciparum and P. knowlesi โ†’ very high parasitemia possible
Duffy antigen P. vivax needs Duffy antigens to invade โ†’ Duffy-negative people resist P. vivax (almost absent in West Africa)
Hb and enzyme polymorphisms Hb S, Hb C, Hb E, ฮฑ- and ฮฒ-thalassemia, G6PD deficiency protect against severe falciparum malaria (infection still occurs). Proposed: enhanced phagocytosis of ring-infected cells (sickle trait, ฮฒ-thal trait, G6PD), โ†“ PfEMP1 display (Hb S trait, Hb C), โ†“ invasion (Hb E trait)

2.17 Malaria โ€” Clinical & Laboratory Findings

Feature Details
Symptoms Fever, chills, rigors, sweating, headache, muscle pain, nausea, diarrhea. Severe: jaundice, splenomegaly, hepatomegaly, shock, bleeding, seizures, coma. Chronic/repeated infection โ†’ massively enlarged spleen
WBC Normal to slightly โ†‘ during fever; neutropenia may develop during chills and rigors
Reticulocytes Decreased in chronic malaria with anemia (inflammation suppresses erythropoiesis)
Severe malaria labs Metabolic acidosis ยท glucose <40 mg/dL ยท โ†‘ lactate ยท โ†‘ creatinine ยท Hb <5 g/dL ยท hemoglobinuria ยท hyperparasitemia

2.18 Malaria โ€” Microscopic Examination (Thick & Thin Films)

Feature Details
Timing Collect before treatment; prepare films as soon as possible after venipuncture
Specimen At least two thick and two thin films from EDTA blood (or capillary puncture)
Stain Wright-Giemsa (Giemsa)
Thick film Concentrates parasites โ†’ ideal for initial screening (detection). Stained with water-based stain without methanol fixation โ†’ RBCs lyse
Thick film prep (Box 25-3) 3 small drops close together; stir ~30 s with slide corner over an area 1โ€“2 cm in diameter; air-dry thoroughly; water-based Giemsa
Thin film Species identification and % parasitemia; methanol-fixed (RBCs preserved)
% Parasitemia Count parasitized RBCs (asexual stages) among 500โ€“2000 RBCs on the thin film โ†’ percentage
Before reporting negative Examine โ‰ฅ300 fields on thick and thin films with the 100ร— objective
Repeat sampling Every 8โ€“12 hours โ€” parasite numbers vary with schizogony timing; one negative set doesn’t rule out malaria
Sensitivity Microscopy detects 5โ€“20 parasites/ยตL (~0.0001% parasitemia)
Pitfall A platelet on top of an RBC can be mistaken for a parasite

2.19 Plasmodium Species on the Thin Film

Feature P. falciparum P. vivax P. ovale P. malariae P. knowlesi
Geography Sub-Saharan Africa, Saudi Arabia, Haiti, Dominican Republic; Asia, SE Asia, South America Asia, South and Central America (~40% of cases worldwide); rare in Africa West Africa, India Worldwide, low frequency; East Africa, India Malaysia; Myanmar, Philippines, Thailand
RBC age infected All ages Reticulocytes Reticulocytes Older RBCs All ages
Infected RBC size Normal Enlarged Enlarged, oval, fringed Normal (not enlarged) Normal*
Stippling Maurer clefts* Schรผffner (all stages except early rings) Schรผffner (all stages, including early rings) None None*
Ring forms Small, easily missed; multiple rings per cell; rings at cell periphery (appliquรฉ) Delicate, red chromatin dot, blue cytoplasm Larger, more ameboid than P. vivax Smaller and wider than P. vivax Like P. falciparum; multiple rings, high parasitemia
Trophozoite Not usually in blood (sequestered) Ameboid, fine light-brown pigment, nearly fills RBC Round, compact Band form across the cell, dark brown pigment Band form like P. malariae
Mature schizont Not usually in blood (sequestered) 12โ€“24 merozoites 8โ€“12 merozoites 6โ€“12 merozoites, rosette around clumped pigment Average 16 merozoites, no rosettes
Gametocyte Crescent/banana-shaped, deep blue cytoplasm, central red chromatin, brownish pigment Round, blue cytoplasm, light-brown pigment (micro-/macrogametocyte) Like P. vivax but smaller Like P. vivax but smaller โ€”
Forms seen in blood Only rings and gametocytes All stages All stages All stages All stages
Erythrocytic cycle 36โ€“48 h 44โ€“48 h 48 h 72 h 24 h
Parasitemia / severity Very high (>50% possible); severe malaria Usually lower; relapse (hypnozoites) Usually benign; relapse (hypnozoites) Usually benign High parasitemia, rapid severe disease

*Maurer clefts and the knowlesi RBC size/stippling entries are from general parasitology references, not stated in Rodak Ch. 25.

2.20 Malaria โ€” Other Tests & Treatment

Feature Details
Fluorescent dyes Sensitive for detection; not useful for speciation
Molecular (PCR) Detection and speciation; helpful in mixed infections, low parasitemia and P. knowlesi
Rapid antigen test BinaxNOW Malaria (FDA-approved): detects P. falciparum histidine-rich protein II (HRP-II) and generic Plasmodium aldolase. Low sensitivity at <100 parasites/ยตL โ†’ always do thick and thin films too
Standard drugs Chloroquine or hydroxychloroquine โ€” except chloroquine-resistant P. falciparum and P. vivax
Resistant strains Combination therapy: atovaquone-proguanil, quinine sulfate + doxycycline or tetracycline, mefloquine; artemether-lumefantrine for resistant P. falciparum
Hypnozoites Primaquine for P. vivax and P. ovale to prevent relapse โ€” test for G6PD deficiency first
Severe anemia Transfusion; exchange transfusion if parasitemia >10%
Urgency P. falciparum and P. knowlesi can be rapidly fatal โ€” treat without delay once diagnosed

2.21 Babesiosis

Feature Details
Organism / vector Intraerythrocytic protozoa, genus Babesia; tick-transmitted. B. microti is the most common U.S. cause (‘Nantucket fever‘, first cluster 1969). Sexual cycle in the tick Ixodes scapularis; asexual cycle in the white-footed mouse (reservoir)
Other transmission Blood transfusion from asymptomatic donors (159 U.S. cases 1979โ€“2009); rarely congenital
Geography B. microti: southern New England, New York, New Jersey, Wisconsin, Minnesota ยท B. duncani: northern California, Washington ยท B. divergens-like: Missouri, Kentucky, Washington ยท B. divergens and B. venatorum: Europe
Clinical Incubation 1โ€“9 weeks; ~โ…“ asymptomatic; mild to severe hemolytic anemia with fever and flu-like symptoms; jaundice, splenomegaly, hepatomegaly possible. Severe disease: ARDS, heart failure, renal failure, DIC โ€” more common >50 years and with asplenia, malignancy, immunosuppression, HIV. Mortality <10%
Labs Hemolytic anemia (โ†“ Hb, โ†‘ retics, โ†“ haptoglobin, bilirubinemia); leukopenia, thrombocytopenia, hemoglobinuria, proteinuria, abnormal renal/liver tests
Film Tiny rings (round, oval, ameboid) with dark purple chromatin and scant cytoplasm around a vacuole; multiple rings per RBC; tetrads (‘Maltese cross’)
vs P. falciparum Babesia: pleomorphic rings, no hemozoin pigment, no gametocytes, tetrads; extracellular forms*
Parasitemia <1% early; up to 80% in asplenic patients
Other tests IgG/IgM indirect immunofluorescent antibody (sensitivity 88โ€“96%); PCR for species identification
Treatment Azithromycin + atovaquone or clindamycin + quinine; exchange transfusion if >10% infected or organ failure; asymptomatic cases usually untreated

*Extracellular Babesia forms are a common textbook differentiator, not stated in Rodak Ch. 25.

2.22 Clostridial Sepsis

Feature Details
Organism Clostridium perfringens โ€” anaerobic gram-positive bacillus; very rapid growth (7-minute doubling time)
Mechanism ฮฑ-toxin with phospholipase C and sphingomyelinase activity hydrolyzes membrane phospholipids โ†’ RBCs become spherical and extremely osmotically fragile โ†’ sudden massive intravascular hemolysis
Findings Dark red plasma and urine; Hct may fall below 10%; can trigger DIC and renal failure
Film Spherocytes, microspherocytes, toxic changes in neutrophils
Risk factors Malignancies (GU, GI, hematologic), solid organ transplant, postpartum/post-abortion, biliary surgery, acute cholecystitis, deep wounds
Prognosis Grave, often fatal despite transfusion, antibiotics, fluids

2.23 Bartonellosis (Carriรณn Disease)

Feature Details
Organism / vector Bartonella bacilliformis โ€” small, pleomorphic intracellular coccobacillus; bite of female sandfly; endemic in Peru, Ecuador, Colombia
Mechanism Bacteria adhere to RBCs; protein deformin causes pits/invaginations in the membrane โ†’ hemolysis
Stage 1 โ€” Oroya fever Acute hemolytic anemia: fever, malaise, headache, chills โ†’ pallor, jaundice, lymphadenopathy; rapid hemolysis, Hct <20% in two thirds
Stage 2 โ€” verruga Chronic stage: skin lesions and warts on extremities, face, trunk
Film Coccobacilli on RBCs (Wright-Giemsa) โ€” up to 80% of RBCs in the acute phase; polychromasia, nRBCs, mild leukocytosis with left shift
Diagnosis Blood culture + film; serology (IFA, immunoblot) ~89% sensitive
Treatment / mortality Transfusion, ciprofloxacin or chloramphenicol. Mortality ~10% hospitalized, ~90% untreated
History Named for Daniel Alcides Carriรณn, a Peruvian medical student who inoculated himself in 1885, linking both stages to one agent

2.24 Drugs, Chemicals, Venoms & Burns

Feature Details
Oxidant drugs/chemicals Oxidative denaturation of Hb โ†’ methemoglobin and Heinz bodies even in normal RBCs: dapsone (leprosy, dermatitis herpetiformis), naphthalene (mothballs). G6PD-deficient cells are especially sensitive (e.g., primaquine)
Other chemicals High levels of arsine hydride, copper, lead
Drug hemolysis labs โ†“ Hb, โ†‘ retics, โ†‘ indirect bilirubin, โ†“ haptoglobin; Heinz bodies with supravital stain only (round blue granules on inner membrane)
Venoms Snakes (some cobras, pit vipers), brown recluse spider (Loxosceles reclusa, L. laeta), multiple bee/wasp stings (โ‰ฅ50). Acute or delayed โ‰ฅ1 day. Mechanisms: direct membrane disruption, complement-mediated lysis, DIC. Severe: renal failure, death
Extensive burns Heating RBCs to 49 ยฐC in vitro causes fragmentation and budding. Burn patients: schistocytes, spherocytes, microspherocytes; damaged cells cleared by spleen within 24 hours
Other burn anemia causes Blood loss (excision/grafting), nutritional deficiency, impaired metabolism, anemia of chronic inflammation
Blood warmers Overheating in malfunctioning warmers โ†’ fragmentation/hemolysis of donor RBCs

3 ยท Visual Memory Hooks

๐Ÿง  MAHA
โ€œSchisto + Low Plts = Micro-Angioโ€ โ€” every MAHA fragments RBCs; platelets consumed in thrombi.
๐Ÿง  DIC vs the rest
โ€œDIC Disturbs the Clotting testsโ€ โ€” PT/PTT prolonged only in DIC; TTP, HUS, HELLP have normal PT/PTT.
๐Ÿง  TTP enzyme
โ€œADAMTS-13 = VWF scissorsโ€ โ€” no scissors โ†’ giant sticky VWF โ†’ platelet clots.
๐Ÿง  TTP treatment
โ€œExchange the Plasma, Exchange the Fateโ€ โ€” 80โ€“90% respond; inherited just needs FFP.
๐Ÿง  HUS
โ€œHamburger โ†’ Bloody diarrhea โ†’ Broken kidneysโ€ โ€” E. coli O157:H7, children, Gb3 (CD77).
๐Ÿง  aHUS
โ€œAtypical = Alternative complementโ€ โ†’ eculizumab.
๐Ÿง  HELLP
โ€œHemolysis, Enzymes (AST), Low Platelets โ€” Pregnantโ€; PT/PTT normal; deliver.
๐Ÿง  Macroangiopathic
โ€œValves slice (schistocytes); Feet squash (no schistocytes)โ€ โ€” platelets normal in both.
๐Ÿง  Cardiac hemolysis
โ€œLeaky valve โ†’ leaky ironโ€ โ€” hemosiderinuria, โ†“ ferritin, microcytosis.
๐Ÿง  Malaria species cycle
โ€œKnowlesi Kwik 24, Vivax & Ovale 48, Malariae 72โ€; falciparum 36โ€“48.
๐Ÿง  RBC age
โ€œVivax & Ovale Very young (retics); Malariae Mature; Falciparum & Knowlesi Feast on allโ€.
๐Ÿง  Enlarged RBC
โ€œBig Vivax, Oval Ovale โ€” both Schรผffnerโ€.
๐Ÿง  Falciparum film
โ€œFalciparum = Few forms: rings and bananas onlyโ€.
๐Ÿง  Malariae
โ€œMalariae = Band and Bouquet (rosette)โ€.
๐Ÿง  Knowlesi
โ€œKnowlesi Knocks off falciparum rings and malariae bandsโ€ โ€” needs PCR.
๐Ÿง  Hypnozoites
โ€œVivax and Ovale Visit againโ€ (relapse) โ†’ primaquine after G6PD test.
๐Ÿง  Thick vs thin
โ€œThick to Tell if present; Thin to Tell which oneโ€.
๐Ÿง  Thick film stain
โ€œThick = No methanol, RBCs Lyseโ€.
๐Ÿง  Duffy
โ€œNo Duffy, No Vivaxโ€.
๐Ÿง  Babesia
โ€œBabesia = Maltese cross, No pigment, No gametocytes, Tick-borneโ€.
๐Ÿง  Clostridium
โ€œClostridium Chews Lipidsโ€ โ€” ฮฑ-toxin (phospholipase C) โ†’ spherocytes, Hct <10%.
๐Ÿง  Burns
โ€œ49 ยฐC Breaks cellsโ€ โ€” schistocytes + microspherocytes within 24 h.

Pattern Triggers

If you seeโ€ฆ Thinkโ€ฆ Becauseโ€ฆ
Schistocytes + platelets 18 ร— 10โน/L + markedly โ†‘ LDH + normal PT/PTT + neuro signs TTP ADAMTS-13 deficiency; coagulation not consumed
Child, bloody diarrhea 1 week ago, schistocytes, โ†‘ creatinine, casts Typical (stx) HUS Shiga toxin damages glomerular endothelium
Schistocytes, thrombocytopenia, prolonged PT/PTT, โ†“ fibrinogen, โ†‘ D-dimer DIC Consumption of factors
Third trimester, preeclampsia, โ†‘ AST, platelets 70, schistocytes, normal PT/PTT HELLP syndrome Placental endothelial dysfunction
Prosthetic valve, schistocytes, normal platelets, hemosiderinuria, โ†“ ferritin Traumatic cardiac hemolytic anemia Turbulence/paravalvular leak
Marathon runner, hemoglobinuria after race, no schistocytes Exercise-induced hemoglobinuria Foot-strike trauma
Traveler from West Africa, multiple small rings, appliquรฉ forms, crescent gametocytes P. falciparum Only rings and gametocytes circulate
Enlarged RBCs with Schรผffner stippling, ameboid trophozoite P. vivax Invades retics
Oval, fringed, enlarged RBCs with Schรผffner dots P. ovale Distinctive oval shape
Band-form trophozoites, rosette schizonts, normal-size RBCs P. malariae 72-hour cycle
Malaysia traveler, falciparum-like rings + malariae-like bands, high parasitemia P. knowlesi 24-hour cycle โ€” urgent
Northeast U.S., tick exposure, tiny pleomorphic rings, tetrads, no pigment Babesiosis (B. microti) Ixodes tick-borne
Postabortion sepsis, Hct 8%, dark red plasma, many spherocytes Clostridial sepsis ฮฑ-toxin phospholipase C
Peru, fever, rapid hemolysis, coccobacilli on RBCs Bartonellosis (Oroya fever) Sandfly-borne B. bacilliformis
Extensive burns, microspherocytes and schistocytes on day 1 Thermal injury hemolysis Heat damage at 49 ยฐC
Dapsone therapy, Heinz bodies, normal G6PD Oxidant drug hemolysis in normal RBCs High-dose oxidant stress

Commonly Confused Pairs

Feature A B
TTP vs HUS Severe โ†“ platelets, neuro, ADAMTS-13 <5โ€“10% Mildโ€“moderate โ†“ platelets, renal failure, Shiga toxin/complement
TTP vs DIC PT/PTT normal PT/PTT prolonged, โ†“ fibrinogen, โ†‘ D-dimer
HELLP vs DIC PT/PTT normal, โ†‘ AST PT/PTT prolonged
Idiopathic vs inherited TTP Autoantibody (IgG) present; plasma exchange No antibody; ADAMTS13 mutation; FFP infusion
Typical vs atypical HUS 90%, Shiga toxin, children, supportive 10%, complement, eculizumab
Cardiac vs exercise hemolysis Schistocytes present Schistocytes absent (rarely present)
Thick vs thin film Detection; no methanol, RBCs lysed Species ID and % parasitemia; methanol-fixed
P. vivax vs P. ovale Enlarged, round; 12โ€“24 merozoites; no stippling in early rings Enlarged, oval, fringed; 8โ€“12 merozoites; stippling in all stages
P. malariae vs P. knowlesi Rosettes, 72 h, low parasitemia No rosettes, 24 h, high parasitemia
P. falciparum vs Babesia Hemozoin pigment, banana gametocytes No pigment, no gametocytes, tetrads
Malaria vs babesiosis vector Female Anopheles mosquito Ixodes tick
Parasite vs platelet over an RBC Ring with chromatin dot inside the RBC Platelet sits on top, with a halo, granular

Timeline Table

Condition / Marker Onset Peak / Key Point Duration Best Exam Use
Stx-HUS renal damage 5โ€“13 days after diarrhea Oliguria Resolves in 1โ€“3 weeks Link to recent gastroenteritis
TTP indirect bilirubin Delayed several days after onset โ€” โ€” LDH rises first
Malaria liver stage 5โ€“16 days after bite Hepatocyte rupture โ†’ merozoites Hypnozoites monthsโ€“years (vivax, ovale) Incubation/relapse
Erythrocytic cycle โ€” Knowlesi 24 h ยท falciparum 36โ€“48 ยท vivax 44โ€“48 ยท ovale 48 ยท malariae 72 Repeating Species ID
Repeat malaria films Every 8โ€“12 hours Parasitemia varies with schizogony Until 3 sets* One negative doesn’t exclude
Babesia incubation 1โ€“9 weeks Symptoms weeks to months โ€” History timing
Burn RBC damage Immediate Cleared by spleen within 24 h โ€” Rodak Q10 timing
Venom hemolysis Acute or delayed โ‰ฅ1 day โ€” โ€” Delayed presentation

*’Three sets’ is CDC practice, not stated in Rodak Ch. 25.

4 ยท Diagnostic Flowcharts

Flowchart 1 โ€” Schistocytes on the film

Schistocytes + hemolysis markers โ†’ Check platelet count
Platelets normal โ†’ Macroangiopathic โ†’ prosthetic/diseased valve (or rarely exercise); check hemosiderinuria, ferritin
Platelets decreased โ†’ MAHA โ†’ check PT/PTT, fibrinogen, D-dimer
PT/PTT prolonged, โ†“ fibrinogen, โ†‘ D-dimer โ†’ DIC
PT/PTT normal โ†’ TTP, HUS or HELLP โ†’ next flowchart
โš ๏ธ Common mistake: calling every schistocyte case ‘DIC’. DIC shows schistocytes in only about half of cases, and TTP/HUS/HELLP have normal PT/PTT.

Flowchart 2 โ€” MAHA with normal PT/PTT

Pregnant, third trimester, โ†‘ AST โ†’ HELLP syndrome โ†’ delivery
Child, bloody diarrhea, acute renal failure โ†’ Typical (stx) HUS โ†’ supportive care
Renal failure, no diarrhea, complement abnormality โ†’ Atypical HUS โ†’ eculizumab
Adult, severe โ†“ platelets (10โ€“30), markedly โ†‘ LDH, ยฑ neuro signs โ†’ TTP โ†’ ADAMTS-13 activity/inhibitor; start plasma exchange urgently
ADAMTS-13 <5โ€“10% + autoantibody โ†’ Idiopathic TTP ยท no antibody โ†’ inherited (Upshaw-Schรผlman) โ†’ FFP
โš ๏ธ Common mistake: waiting for the ADAMTS-13 result before treating โ€” TTP needs plasma exchange quickly.

Flowchart 3 โ€” Suspected malaria

Fever + travel to endemic area โ†’ Collect EDTA blood before treatment
Thick films (water-based Giemsa, no methanol) โ†’ Screen for parasites
Thin films (methanol-fixed) โ†’ Identify species + count % parasitemia (500โ€“2000 RBCs)
Negative after โ‰ฅ300 fields at 100ร— โ†’ Repeat every 8โ€“12 h; add rapid antigen test/PCR
Positive โ†’ Report species and parasitemia urgently; falciparum/knowlesi = emergency
โš ๏ธ Common mistake: reporting a negative result from one set of films, or mistaking a platelet on an RBC for a ring form.

Flowchart 4 โ€” Identifying the Plasmodium species on the thin film

Only small rings (multiple, appliquรฉ) + crescent gametocytes; normal RBC size โ†’ P. falciparum
Enlarged RBC, Schรผffner stippling, ameboid trophozoite, 12โ€“24 merozoites โ†’ P. vivax
Enlarged, oval, fringed RBC, stippling in all stages, 8โ€“12 merozoites โ†’ P. ovale
Normal RBC size, band forms, rosette schizont (6โ€“12) โ†’ P. malariae
Falciparum-like rings + malariae-like bands, ~16 merozoites, no rosette, Malaysia โ†’ P. knowlesi โ†’ PCR
โš ๏ธ Common mistake: calling P. knowlesi ‘P. malariae’ โ€” the 24-hour cycle makes it dangerous.

Flowchart 5 โ€” Intracellular ring forms: malaria or Babesia?

Rings inside RBCs โ†’ Look for pigment, gametocytes, tetrads, history
Hemozoin pigment or crescent/round gametocytes โ†’ Malaria
No pigment, no gametocytes, pleomorphic rings, tetrads (Maltese cross) โ†’ Babesia
History โ†’ Mosquito/travel โ†’ malaria ยท tick exposure, NE U.S., asplenia, transfusion โ†’ Babesia
Confirm โ†’ Babesia: IFA serology, PCR ยท Malaria: rapid antigen, PCR
โš ๏ธ Common mistake: diagnosing P. falciparum from multiple small rings alone โ€” Babesia also has multiple rings per cell.

Flowchart 6 โ€” Spherocytes with sudden massive hemolysis

Spherocytes/microspherocytes + dark red plasma and urine โ†’ Check DAT and history
DAT positive โ†’ Immune hemolysis (next chapter)
DAT negative + sepsis risk (postabortion, GI cancer, biliary surgery) โ†’ Clostridial sepsis โ†’ blood cultures, urgent antibiotics
DAT negative + extensive burns โ†’ Thermal injury
DAT negative + snake/spider/multiple stings โ†’ Venom
โš ๏ธ Common mistake: attributing all spherocytes to HS or autoimmune hemolysis โ€” acquired toxins and heat produce them too.

5 ยท 25 High-Yield Facts

# Fact
1 In extrinsic hemolytic anemias the RBCs are structurally and functionally normal.
2 Intravascular RBC fragmentation is a feature of all microangiopathic hemolytic anemias.
3 Schistocytes plus thrombocytopenia characterize microangiopathic hemolytic anemia.
4 TTP is caused by severe deficiency of ADAMTS-13, the VWF-cleaving protease.
5 Idiopathic TTP is due to autoantibodies, usually IgG, that inhibit ADAMTS-13.
6 Inherited TTP (Upshaw-Schรผlman syndrome) is caused by ADAMTS13 gene mutations.
7 In TTP, platelets are typically 10โ€“30 ร— 10โน/L and LDH is markedly increased.
8 PT and PTT are usually normal in TTP, HUS and HELLP but prolonged in DIC.
9 About 80โ€“90% of idiopathic TTP patients respond to plasma exchange.
10 Typical HUS (90%) follows Shiga toxinโ€“producing E. coli such as O157:H7 infection, mostly in children.
11 Shiga toxin binds the Gb3 (CD77) receptor on endothelial cells.
12 Atypical HUS is caused by uncontrolled activation of the alternative complement pathway.
13 HELLP syndrome shows hemolysis, elevated AST, platelets below 100 ร— 10โน/L and normal PT/PTT.
14 DIC shows prolonged PT/PTT, decreased fibrinogen and increased D-dimer; schistocytes in about half.
15 Traumatic cardiac hemolysis shows schistocytes with a normal platelet count.
16 Chronic hemoglobinuria from valve hemolysis causes hemosiderinuria and low serum ferritin.
17 Exercise-induced hemoglobinuria usually shows no schistocytes and is a diagnosis of exclusion.
18 P. vivax and P. ovale form hypnozoites that cause relapse; primaquine requires prior G6PD testing.
19 P. vivax and P. ovale invade reticulocytes; P. malariae older cells; P. falciparum and P. knowlesi all ages.
20 Duffy-negative individuals are resistant to P. vivax.
21 Only ring forms and crescent-shaped gametocytes of P. falciparum are usually seen in peripheral blood.
22 P. knowlesi has a 24-hour erythrocytic cycle; P. malariae has a 72-hour cycle.
23 Thick films are for detection (no methanol fixation); thin films are for species ID and parasitemia.
24 Babesia shows tetrads (Maltese cross) and lacks hemozoin pigment and gametocytes.
25 Clostridium perfringens ฮฑ-toxin (phospholipase C) causes massive intravascular hemolysis with spherocytes.
โญ EXAM TIP โ€” The single most testable pattern

Schistocytes + โ†“ platelets: check PT/PTT. Prolonged โ†’ DIC. Normal โ†’ TTP (adult, severe โ†“ platelets, โ†‘โ†‘ LDH, neuro), HUS (child, diarrhea, kidneys) or HELLP (pregnancy, โ†‘ AST). Schistocytes + normal platelets โ†’ prosthetic valve. For malaria, remember the RBC size, stippling, forms present and cycle length for each species.

Quick Interpretation Table

Lab Finding Clinical Interpretation
24-year-old back from Ghana; fever; Hb 8.7; multiple small rings, appliquรฉ forms; banana gametocyte on thick film P. falciparum malaria (Rodak case study)
Seizure, Hb 7.8, platelets 18, schistocytes, helmet cells, โ†‘โ†‘ LDH, normal PT/PTT TTP (Rodak Q11)
Rhode Island vacation, ameboid rings and tetrads, platelets 134 Babesiosis (Rodak Q9)
ADAMTS-13 activity 3%, inhibitor present Idiopathic (autoimmune) TTP
Platelets 60, creatinine โ†‘, RBC casts, bloody diarrhea 7 days ago, child Typical (stx) HUS
Platelets 45, AST 900 U/L, normal PT/PTT, 34 weeks pregnant HELLP syndrome (severe โ€” platelets <50)
Mechanical valve, normal platelets, schistocytes, ferritin 8 ng/mL, microcytosis Traumatic cardiac hemolysis with iron deficiency
Parasitemia 12% P. falciparum, Hb 4.5 g/dL Severe malaria โ€” consider exchange transfusion

๐ŸŽด Flashcards โ€” Active Recall Practice

How it works: tap the card to flip it. Then mark it โœ“ Knew It or โœ— Review Again (buttons unlock after flipping). Use ๐Ÿ”€ Shuffle to randomize and ๐Ÿ Finish anytime โ€” your summary appears at the end, and you can drill only the cards you missed.

๐Ÿ“ Practice Quiz โ€” Test Your Knowledge

How it works: tap an answer for each case. You’ll get instant feedback with the full explanation and the examiner’s trap. Your final score appears once all 10 are answered.

๐Ÿชค Trap Questions โ€” Beat the Examiner

Harder on purpose. Each question targets a real misconception. After answering you’ll see the correct reasoning, the trap explained, why the examiner wrote it, and the wrong answer most students choose.

8 ยท Rapid Revision Sheet

๐Ÿ“– READ THIS 2 HOURS BEFORE YOUR EXAM

MAHA Basics

  • Normal RBCs, outside injury
  • Shearing by microthrombi โ†’ schistocytes
  • Platelets consumed โ†’ โ†“
  • TTP ยท HUS ยท HELLP ยท DIC
  • PT/PTT prolonged only in DIC

TTP

  • ADAMTS-13 โ†“ โ†’ ULVWF โ†’ plateletโ€“VWF thrombi
  • Adults, 4th decade, F > M
  • Hb 8โ€“10 ยท plts 10โ€“30 ยท LDH โ†‘โ†‘
  • ADAMTS-13 <5โ€“10% (idiopathic/inherited)
  • Plasma exchange 80โ€“90% ยท โ…“ relapse ยท rituximab

TTP Types

  • Idiopathic: IgG autoantibody
  • Secondary: pregnancy, HSCT, HIV, cancer, quinine, ticlopidine, trimethoprim
  • Inherited: Upshaw-Schรผlman, ADAMTS13 โ†’ FFP

HUS

  • Typical 90%: STEC O157:H7, Shigella, kids
  • Bloody diarrhea โ†’ 5โ€“13 d renal failure
  • Stx-1/Stx-2 โ†’ Gb3 (CD77)
  • Atypical 10%: alternative complement โ†’ eculizumab
  • Plts mildโ€“mod โ†“ ยท creatinine โ†‘ ยท casts

HELLP & DIC

  • HELLP: <1% pregnancies, 10โ€“20% severe preeclampsia
  • Plts <100 (<50 worse) ยท AST โ†‘โ†‘ ยท PT/PTT normal
  • Deliver ยท mortality mother 3โ€“5%, fetus 9โ€“24%
  • DIC: PT/PTT โ†‘, fibrinogen โ†“, D-dimer โ†‘
  • Schistocytes in ~ยฝ of DIC

Macroangiopathic

  • Valves: schistocytes, normal plts
  • Paravalvular leak โ†’ severe
  • Hemosiderinuria, โ†“ ferritin โ†’ microcytic
  • Exercise: no schistocytes, โ†“ Hp, hemoglobinuria
  • Diagnosis of exclusion

Malaria Biology

  • Female Anopheles โ†’ sporozoites โ†’ liver (5โ€“16 d)
  • Ring โ†’ trophozoite โ†’ schizont โ†’ merozoites
  • Hypnozoites: vivax, ovale โ†’ primaquine (G6PD!)
  • Retics: vivax/ovale ยท old: malariae ยท all: falci/knowlesi
  • Duffy-neg resist vivax

Species ID

  • Falci: rings + bananas only, multiple rings, 36โ€“48 h
  • Vivax: big RBC, Schรผffner, ameboid, 12โ€“24 mz, 44โ€“48 h
  • Ovale: oval fringed, stippling all stages, 8โ€“12, 48 h
  • Malariae: bands, rosette 6โ€“12, 72 h
  • Knowlesi: falci rings + bands, 16 mz, 24 h

Malaria Lab

  • EDTA before treatment ยท 2 thick + 2 thin
  • Thick: water Giemsa, no methanol โ†’ detect
  • Thin: methanol โ†’ species + % (500โ€“2000 RBCs)
  • โ‰ฅ300 fields at 100ร— ยท repeat q8โ€“12 h
  • BinaxNOW: HRP-II + aldolase; <100/ยตL weak

Other Infections & Injury

  • Babesia: Ixodes, tetrads, no pigment/gametocytes
  • Babesia up to 80% asplenic ยท IFA ยท PCR
  • C. perfringens: ฮฑ-toxin, spherocytes, Hct <10%
  • Bartonella: sandfly, Peru, Oroya fever
  • Burns: 49 ยฐC, schistocytes + microspherocytes <24 h

9 ยท Final Memory Map

  • โš”๏ธ EXTRINSIC NONIMMUNE HEMOLYSIS
    • Microangiopathic (MAHA)
      • TTP โ€” ADAMTS-13, plasma exchange
      • HUS โ€” Shiga toxin (90%) / complement (10%)
      • HELLP โ€” pregnancy, โ†‘ AST, delivery
      • DIC โ€” PT/PTT โ†‘, fibrinogen โ†“, D-dimer โ†‘
    • Macroangiopathic
      • Traumatic cardiac โ€” schistocytes, normal platelets, iron loss
      • Exercise-induced โ€” no schistocytes, exclusion diagnosis
    • Malaria
      • Life cycle, hypnozoites (vivax, ovale)
      • Anemia: lysis, splenic removal, marrow suppression
      • 5 species โ€” size, stippling, forms, cycle
      • Thick vs thin films, rapid antigen, PCR
      • Chloroquine / combinations / primaquine / exchange
    • Babesiosis
      • Ixodes tick, B. microti, transfusion
      • Tetrads, no pigment or gametocytes
      • Asplenia โ†’ severe
    • Bacterial
      • Clostridial sepsis โ€” ฮฑ-toxin, spherocytes
      • Bartonellosis โ€” Oroya fever, deformin
    • Other RBC Injury
      • Oxidant drugs/chemicals โ€” Heinz bodies
      • Venoms โ€” snakes, brown recluse, stings
      • Burns โ€” 49 ยฐC, microspherocytes



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