Heme 06: Hemolytic Anemia And Applications

Front 1

What does hemolytic anemia result in?

Back 1

- Loss of RBC mass
- Release of cellular contents

Front 2

What are the inherited / intrinsic disorders that cause Hemolytic Anemia?

Back 2

- RBC membrane disorders
- RBC enzyme deficiencies
- Hemoglobinopathies

Front 3

What are the acquired / extrinsic disorders that cause Hemolytic Anemia?

Back 3

- Auto-immune (Ab-mediated) hemolysis (warm and cold)
- Mechanical trauma
- Infections (malaria)
- Chemical
- Splenic sequestration

Front 4

Where does pathologic hemolysis occur?

Back 4

- Extravascular: most commonly, spleen >>> liver, BM
- Intravascular: less common, within the vessels
- Both

Front 5

What happens to the RBCs that are not deformable?

Back 5

- They are unable to squeeze through endothelium
- Get caught outside of sinusoid which is rich in macrophages
- RBCs that can't get inside of the sinusoid get chewed up and engulfed by macrophage

Front 6

Which types of hemolytic anemias have RBCs hemolyzed in the extravascular space?

Back 6

- RBC membrane deficiencies
- RBC enzyme deficiencies*
- Sickle cell anemia*
- Thalassemias
- Auto-immune hemolysis (by antibodies)
(* also intravascular hemolysis)

Front 7

Which types of hemolytic anemias have RBCs hemolyzed in the intravascular space?

Back 7

- RBC enzyme deficiencies*
- Sickle cell anemia*
- Auto-immune hemolysis (by complement)
- PNH
- Mechanical
- Malaria
(* also extravascular hemolysis)

Front 8

What are the morphologic characteristics in hemolytic anemia?

Back 8

Normocytic anemia (normal in size)

Front 9

What are the lab findings in hemolytic anemia?

Back 9

- Reticulocytosis
- ↑ LDH, AST, and K+ (release of cellular contents)
- Bilirubinemia
- Hemoglobinemia
- Hemoglobinuria
- Hemosiderinuria

Front 10

What type of hemolysis has more prominent Hemoglobinemia? What happens to the free Hb?

Back 10

- More pronounced in intravascular hemolysis
- Scavenged by Haptoglobin

Front 11

What are the types of Bilirubinemia?

Back 11

- Unconjugated bilirubinemia (indirect)
- Conjugated bilirubinemia w/ liver disease

Front 12

What type of hemolysis has more prominent Hemoglobinuria?

Back 12

- Mostly observed in intravascular processes
- Hb not scavenged by Haptoglobin

Front 13

What type of hemolysis has more prominent Hemosiderinuria? What happens?

Back 13

- Mostly observed in intravascular processes
- Iron deposits in renal epithelium, then shed in urine

Front 14

How do lab tests assess the presence / concentration of Hb or heme in the blood or urine? What is the laboratory caveat with hemolysis?

Back 14

Spectrophotometry using Beer's law:
A = ε * L * c
- Absorbance is proportional to concentration

- Spectrophotometer will absorb the red from the hemolyzed specimen, so it is less accurate

- Hemoglobin absorbs at measured wavelengths, therefore, many assays produce falsely increased results in the setting of hemolysis

- Could be a defect of poor phlebotomy (shearing the cells) or because they really had a hemolytic event

Front 15

What other lab test is a marker of hemolysis? How do you tell if it is a real hemolysis or false hemolysis?

Back 15

Hyperkalemia
- If you suspect that it is a phlebotomy-induced hemolysis you should do another lab draw to see if the same results occur or not

Front 16

What are the clinical features of hemolysis?

Back 16

- Anemia
- Hyperbilirubinemia

- Other characteristic symptoms are related to the underlying pathology causing the hemolysis (eg, vaso-occlusive crises in sickle cell anemia)

Front 17

What is a major determinant of the symptoms in hemolytic anemia?

Back 17

Acuity of hemolysis:
- Most important question is how does patient's Hb and Hematocrit compare to baseline
- Young patients w/ chronic hemolytic conditions (eg, sickle cell, thalassemia, pyruvate kinase deficiency)

Front 18

How low of a hemoglobin can a young patient with chronic hemolytic anemia have and still not have symptoms?

Back 18

- Patients: 6-7 g/dL
- Normal: 12-16 g/dL

Front 19

What is the approximate hemoglobin conc. when there is <20% hemolysis? Symptoms?

Back 19

> 11 g/dL
Restlessness

Front 20

What is the approximate hemoglobin conc. when there is 20-30% hemolysis? Symptoms?

Back 20

- 10-11 g/dL
- Anxiety, dyspnea w/ exertion
- Orthostatic hypotension
- Tachycardia w/ exertion

Front 21

What is the approximate hemoglobin conc. when there is 30-40% hemolysis? Symptoms?

Back 21

- 8-9 g/dL
- Syncope
- Orthostatic hypotension
- Tachycardia at rest

Front 22

What is the approximate hemoglobin conc. when there is >40% hemolysis? Symptoms?

Back 22

- <8 g/dL
- Confusion
- Shock

Front 23

What are the lab signs of hyperbilirubinemia in hemolytic anemia?

Back 23

- Increased production of unconjugated (or indirect) bilirubin
- Direct bilirubin level is normal
- Rare to have indirect bilirubin >5 mg/dL d/t hemolysis in absence of concurrent liver disease

Front 24

What are the clinical signs and when can you detect the clinical signs of hyperbilirubinemia in hemolytic anemia?

Back 24

- Jaundice is detectable in most fair-skinned individuals when bilirbuin exceeds 2.5 mg/dL
- Scleral icterus can be detected by experienced physicians when bilirubin exceeds 1.5 mg/dL
- Increased risk of bilirubin gallstones (pigmented)

Front 25

What are the rare complications of hemolytic anemia?

Back 25

- Pigment induced kidney injury
- Folate deficiency d/t increased utilization
- Increased risk of venous and arterial thrombosis related, including venous thrombosis of atypical sites (portal vein, cerebral venous sinus)

Front 26

What can cause kidney injury in hemolytic anemia?

Back 26

- Heme pigment can cause tubular obstruction, direct cellular injury, and vasoconstriction resulting in decreased medullary blood flow
- Urinalysis shows hemoglobinuria w/o RBCs

Front 27

Which types of hemolytic anemia cause splenomegaly and hepatomegaly related to extra-medullary hematopoiesis?

Back 27

- Thalassemia
- PK deficiency
- Hereditary spherocytosis

Front 28

Which types of hemolytic anemia causes skeletal changes related to expansion of marrow, "chipmunk facies", convex bones?

Back 28

β-thalassemia major

Front 29

Which types of hemolytic anemia causes asplenia?

Back 29

Sickle Cell Anemia

Front 30

Which types of hemolytic anemia causes microangiopathic hemolytic anemia?

Back 30

- TTP (Thrombotic thrombocytopenic Purpura)
- HUS (Hemolytic-Uremic Syndrome)
- DIC (Disseminated Intravascular Coagulation)
- Malignant HTN
- CREST syndrome
- Vasculitis
- HELLP syndrome

Front 31

What does microangiopathic hemolytic anemia cause?

Back 31

Microvascular infarction causes:
- Acute kidney injury
- Liver disease
- Abdominal pain
- Fever
- Mental status changes
- Thrombocytopenia
- Rash
- Hemorrhagic diarrhea

Front 32

Case 1: 35 yo female presents to establish care. She is a poor historian and vaguely recalls a diagnosis of anemia as a child. She denies fatigue, headache, SOB, difficulty w/ exertion, palpitations, or abdominal discomfort. She has mild jaundice, splenomegaly, and laparoscopic surgical scars on abdomen. Hb is 9.4 g/dL. PB smear shows abnormal RBCs.

What RBC parameters are associated with this abnormal RBC morphology?

Back 32

- Increased MCHC
- Increased RDW
- Decreased MCV
- Decreased RBC count (anemic)

Front 33

Case 1: 35 yo female presents to establish care. She is a poor historian and vaguely recalls a diagnosis of anemia as a child. She denies fatigue, headache, SOB, difficulty w/ exertion, palpitations, or abdominal discomfort. She has mild jaundice, splenomegaly, and laparoscopic surgical scars on abdomen. Hb is 9.4 g/dL. PB smear shows abnormal RBCs.

This RBC morphologic abnormality may be identified in what kind of conditions?

Back 33

Acquired (auto-immune hemolytic anemia) and Inherited (hereditary spherocytosis)

Front 34

Case 1: 35 yo female presents to establish care. She is a poor historian and vaguely recalls a diagnosis of anemia as a child. She denies fatigue, headache, SOB, difficulty w/ exertion, palpitations, or abdominal discomfort. She has mild jaundice, splenomegaly, and laparoscopic surgical scars on abdomen. Hb is 9.4 g/dL. PB smear shows abnormal RBCs.

What lab test is most important in differentiating the causes of this RBC morphologic abnormality?

Back 34

Direct Antiglobulin Test - distinguishes between inherited (eg, hereditary spherocytosis) and acquired (eg, auto-immune hemolytic anemia) causes

Front 35

What test can identify spherocytes besides a PB smear?

Back 35

Osmotic fragility / lysis test
- Spherocytes are more fragile in hypotonic solutions
- This test tells you that there are spherocytes present

Front 36

What are the characteristics of spherocytes?

Back 36

- Normal sized RBCs
- Increased Hb concentration
- Less flexible, get trapped in spleen

Front 37

What disorders have spherocytes?

Back 37

- Hereditary spherocytosis
- Auto-immune hemolytic anemia (AIHA): cold and warm

Front 38

Case 1: 35 yo female presents to establish care. She is a poor historian and vaguely recalls a diagnosis of anemia as a child. She denies fatigue, headache, SOB, difficulty w/ exertion, palpitations, or abdominal discomfort. She has mild jaundice, splenomegaly, and laparoscopic surgical scars on abdomen. Hb is 9.4 g/dL. PB smear shows abnormal RBCs.

What previous surgeries are the abdominal scars most likely secondary to?

Back 38

Cholecystectomy (or partial splenectomy)

Front 39

Case 1: 35 yo female presents to establish care. She is a poor historian and vaguely recalls a diagnosis of anemia as a child. She denies fatigue, headache, SOB, difficulty w/ exertion, palpitations, or abdominal discomfort. She has mild jaundice, splenomegaly, and laparoscopic surgical scars on abdomen. Hb is 9.4 g/dL. PB smear shows abnormal RBCs.

The pathophysiology of this patient's disease is best characterized as?

Back 39

Congenital RBC membrane disorder

Front 40

What are the congenital RBC membrane disorders?

Back 40

- Hereditary spherocytosis
- Hereditary elliptocytosis

Front 41

What is the pathogenesis of hereditary spherocytosis?

Back 41

- Membranes of patients form little membrane vesicles
- When they get to spleen the macrophages remove the micro-vesicles
- Cells lose membrane but not cytoplasm

Front 42

What is the most common inherited hemolytic anemia in the US? How is it inherited?

Back 42

Hereditary Spherocytosis
- 1/5000
- 75% autosomal dominant
- 25% sporadic (recessive and new mutations, compound heterozygosity)

Front 43

What are the primary defects causing hereditary spherocytosis?

Back 43

- Ankyrin (most common)
- Spectrin
- Band 3

- Most patients have deficiencies in both ankyrin AND spectrin d/t a protein imbalance

Front 44

What are the clinical findings of hereditary spherocytosis?

Back 44

- Wide variability in severity of hemolysis
- Sometimes an incidental finding
- Mild anemia
- Moderate to severe hemolysis
- Splenomegaly

Front 45

How do you treat hereditary spherocytosis?

Back 45

- Depends on clinical severity
- Manage chronic hemolysis (may require transfusions or splenectomy)
- Treat gallstones and jaundice w/ cholecystectomy (usually by age 25-30)
- Managing aplastic crisis (mostly by treating Parvovirus B19)
- Splenectomy (complete for adults and partial for children under age 6)

Front 46

At what age is it safe to do a full splenectomy vs partial splenectomy? Why?

Back 46

- Before age 6 do a partial splenectomy
- Full splenectomy is discouraged in children <6 because of increased incidence of encapsulated organism infections (eg, strep pneumo)
- But the partial splenectomy is still helpful because it decreases need for transfusions

Front 47

Case 1b: Patient with similar findings and laboratories presents to ED w/ new onset jaundice, fatigue, and shortness of breath. BP 142/88, P 100bpm, R 18, T 98.6, and SaO2 97%. Bilirubin is 3 mg/dL (normal 0.2-1.2 mg/dL). They have the same PB smear as previous patient.

Results of DAT are shown. What is the most likely cause?

Back 47

Classically a young woman with lupus (auto-immune disorder) causing Auto-Immune Hemolytic Anemia

Front 48

Case 1b: Patient with similar findings and laboratories presents to ED w/ new onset jaundice, fatigue, and shortness of breath. BP 142/88, P 100bpm, R 18, T 98.6, and SaO2 97%. Bilirubin is 3 mg/dL (normal 0.2-1.2 mg/dL). They have the same PB smear as previous patient.

What is the most appropriate therapeutic option for this patient?

Back 48

Corticosteroids to treat Auto-Immune Hemolytic Anemia

Front 49

What is the pathophysiology responsible for Auto-Immune Hemolytic Anemias (AIHAs)?

Back 49

- Host antibodies reactive w/ autologous RBCs
- Shortened in vivo RBC survival

Front 50

How do you distinguish the different types of Auto-Immune Hemolytic Anemias (AIHAs)?

Back 50

- Warm auto-Abs → 37°C optimal temperature of activity
- Cold auto-Abs → 0-5°C optimal temperature range of activity

Front 51

Which type of Auto-Immune Hemolytic Anemia (AIHA) is more common? What are the causes?

Back 51

Warm auto-antibody type (~80%):
- Idiopathic (primary)
- Secondary

Front 52

What disorders are associated with secondary Warm Auto-Immune Hemolytic Anemias (AIHAs)?

Back 52

- Lymphoproliferative disorders (excessive production of Abs against RBCs)
- Auto-immune disorders (eg, Lupus)
- Non-hematopoietic neoplasms (eg, ovarian cancer)
- Drugs (eg, α-methlydopa, cephalosporins)

Front 53

Which drugs are associated with secondary Warm Auto-Immune Hemolytic Anemias (AIHAs)?

Back 53

- α-methyldopa
- Cephalosporins

Front 54

Which type of Auto-Immune Hemolytic Anemia (AIHA) is less common? What are the causes?

Back 54

Cold auto-antibody type (~20%):
- Idiopathic (primary)
- Secondary

Front 55

What disorders are associated with secondary Cold Auto-Immune Hemolytic Anemias (AIHAs)?

Back 55

- Post-infectious (eg, infections mononucleosis, Mycoplasma)
- Lymphoproliferative disorders (excessive production of Abs against RBCs)

Front 56

What is the pathogenesis of Warm Auto-Immune Hemolytic Anemias (AIHAs)?

Back 56

Extravascular Hemolysis
- Ab mediated (IgG1 and IgG3) OR
- Complement mediated (classical pathway)
- Leads to Spherocyte production

Front 57

What is the pathogenesis of Cold Auto-Immune Hemolytic Anemias (AIHAs)?

Back 57

- IgM binds in cold
- IgM-mediated agglutination
- RBC agglutination impedes blood flow in superficial distal vessels
- IgM and complement mediated RBC injury (extravascular hemolysis in liver > spleen)

Front 58

What are the symptoms of Warm Auto-Immune Hemolytic Anemias (AIHAs)?

Back 58

- Symptoms of anemia
- Mild → severe (w/ massive hemolysis)
- Organomegaly

Front 59

What are the symptoms of Cold Auto-Immune Hemolytic Anemias (AIHAs)?

Back 59

Acute or chronic form
- Acute form occurs 2-3 weeks into infectious illness
- Follows cold exposure

Symptoms of anemia
- Mild → severe (w/ massive hemolysis)

Acrocyanosis (bluish/purplish skin)
- Raynaud phenomenon

Front 60

Case 2: 17 yo AA male presents w/ persistent fatigue following recent sinus infection. Patient was started on trimethoprim-sulfamethaxazole 7 days ago and has since had resolution of fevers. Physical exam reveals scleral icterus. Hb 8.1 g/dL. MCV 105 fL. Absolute reticulocyte count 185,000 / µL (normal 30,000-82,000/µL). Bilirubin 7.3 mg/dL (normal <1.2). Direct bilirubin normal.

What genetic mutation most likely explains this patient's symptoms and lab findings?

Back 60

Glucose 6-Phosphate Dehydrogenase

Front 61

Case 2: 17 yo AA male presents w/ persistent fatigue following recent sinus infection. Patient was started on trimethoprim-sulfamethaxazole 7 days ago and has since had resolution of fevers. Physical exam reveals scleral icterus. Hb 8.1 g/dL. MCV 105 fL. Absolute reticulocyte count 185,000 / µL (normal 30,000-82,000/µL). Bilirubin 7.3 mg/dL (normal <1.2). Direct bilirubin normal.

RBC abnormality observed in PB smear is secondary to what?

Back 61

Mononuclear cell phagocytosis of denatured protein (Heinz bodies made of denatured Hb d/t deficiency of G6PD)

Front 62

Case 2: 17 yo AA male presents w/ persistent fatigue following recent sinus infection. Patient was started on trimethoprim-sulfamethaxazole 7 days ago and has since had resolution of fevers. Physical exam reveals scleral icterus. Hb 8.1 g/dL. MCV 105 fL. Absolute reticulocyte count 185,000 / µL (normal 30,000-82,000/µL). Bilirubin 7.3 mg/dL (normal <1.2). Direct bilirubin normal.

Based on the lab findings, what is true about the patient's BM?

Back 62

- Erythroid precursors outnumber the granulocytic precursors
- This is true of all hemolytic anemias because they will rev up production of erythroid precursors to compensate for those that are being hemolysed

Front 63

Case 2: 17 yo AA male presents w/ persistent fatigue following recent sinus infection. Patient was started on trimethoprim-sulfamethaxazole 7 days ago and has since had resolution of fevers. Physical exam reveals scleral icterus. Hb 8.1 g/dL. MCV 105 fL. Absolute reticulocyte count 185,000 / µL (normal 30,000-82,000/µL). Bilirubin 7.3 mg/dL (normal <1.2). Direct bilirubin normal.

What is the most appropriate treatment at this time?

Back 63

Stop trimethoprim-sulfamethaxaole (this is causing the oxidative stress that his G6PD deficiency can't keep up with → Heinz bodies → macrophages make bite cells)

Front 64

Case 2: 17 yo AA male presents w/ persistent fatigue following recent sinus infection. Patient was started on trimethoprim-sulfamethaxazole 7 days ago and has since had resolution of fevers. Physical exam reveals scleral icterus. Hb 8.1 g/dL. MCV 105 fL. Absolute reticulocyte count 185,000 / µL (normal 30,000-82,000/µL). Bilirubin 7.3 mg/dL (normal <1.2). Direct bilirubin normal.

What kind of disorder is this?

Back 64

Congenital RBC enzyme disorder (G6PD)

Front 65

Case 2: 17 yo AA male presents w/ persistent fatigue following recent sinus infection. Patient was started on trimethoprim-sulfamethaxazole 7 days ago and has since had resolution of fevers. Physical exam reveals scleral icterus. Hb 8.1 g/dL. MCV 105 fL. Absolute reticulocyte count 185,000 / µL (normal 30,000-82,000/µL). Bilirubin 7.3 mg/dL (normal <1.2). Direct bilirubin normal.

What should you counsel the patient about?

Back 65

Similar episodes with overwhelming infections
- They have a tendency to hemolyze if they are in the presence of something that stimulates oxidative stress
- Normal machinery (G6PD) can deal w/ oxidant stress but those that have deficiency are susceptible to insults

Front 66

What pathways can glucose go down?

Back 66

- 90% for Glycolysis
- 10% for Pentose Phosphate Pathway

Front 67

What regulates the partitioning into glycolysis vs the pentose phosphate pathway?

Back 67

NADPH

Front 68

What pathway does a deficiency of Glucose 6-Phosphate Dehydrogenase affect?

Back 68

Pentose Phosphate Pathway

Front 69

What is the congenital RBC enzyme disorder to know? Implications?

Back 69

Glucose 6-Phosphate Dehydrogenase Deficiency
- Defect in the pathway responsible for reducing oxidants
- Causes a build up of Glucose 6-Phosphate
- Decreased glutathione production
- Inability to reduce oxidant stressors

Front 70

What are some oxidant stressors that can affect a patient with Glucose 6-Phosphate Dehydrogenase Deficiency?

Back 70

- Infections
- Fava benas
- Drugs: dapsone, sulfonamides, primaquine, nitrofurantoin, and quinolones

Front 71

What happens to RBCs in Glucose 6-Phosphate Dehydrogenase Deficiency?

Back 71

- Increased susceptibility to oxidant stress
- RBCs lead to hemolytic anemia (extravascular process)

Front 72

How common is Glucose 6-Phosphate Dehydrogenase Deficiency? How is it obtained?

Back 72

- 400 million affected
- Common in malarial endemic areas
- X-linked disorder

Front 73

Which Glucose 6-Phosphate Dehydrogenase Deficiency variant is most common in USA? Implications?

Back 73

G6PD A-
- Moderate hemolysis
- Found in 11% of AAs

G6PD A and B are both normal and do not cause hemolysis

Front 74

How does a Glucose 6-Phosphate Dehydrogenase Deficiency affect males?

Back 74

X-linked
- Normal male will have 100% G6PD activity
- Deficient male will have 5-15% GDPD activity as RBC ages

Front 75

How does a Glucose 6-Phosphate Dehydrogenase Deficiency affect females?

Back 75

X-linked
- Normal female will have 100% G6PD activity
- Female carrier will have ~50% G6PD activity because X inactivation leads to 2 separate RBC populations

Front 76

What is the hematologic impact of dapsone (oxidant stressor) on a normal person?

Back 76

When you give them oxidant stressor, normal patient deals with it just find, Hb doesn't change

Front 77

What is the hematologic impact of dapsone (oxidant stressor) on a homozygous patient (male w/ G6PD deficiency)?

Back 77

Oxidant stress causes Hb to rapidly dip, eventually they recover

Front 78

What is the hematologic impact of dapsone (oxidant stressor) on a heterozygous female with 50% activity?

Back 78

Normal Hb with small dip

Front 79

What is the hematologic impact of dapsone (oxidant stressor) on a heterozygous female with greater expression of the X chromosome with low G6PD activity?

Back 79

May have marked hemolysis w/ big drop in Hb

Front 80

What are the features of G6PD A-?

Back 80

- 11% of African-American males
- Leads to an unstable enzyme (100% activity in new RBCs but only 5-15% activity in old RBCS)
- Self-limited hemolysis (old RBCs hemolyze, reticulocytes and new RBCs do not hemolyze)

Front 81

How do we diagnose Glucose 6-Phosphate Dehydrogenase Deficiency?

Back 81

PB smear shows bite cells

Front 82

Case 3: 42 yo AA male presents w/ headaches and altered mental status. PMH shows end-stage kidney disease secondary to long-standing HTN. BP 220/150 mmHg. Urinalysis shows 4+ proteinuria, +hemoglobinuria, but no RBCs. Elevated creatinine. PB smear shows schistocytes / fragments.

What lab abnormality is likely to be also present in this patient?

Back 82

Decreased haptoglobin

Front 83

Case 3: 42 yo AA male presents w/ headaches and altered mental status. PMH shows end-stage kidney disease secondary to long-standing HTN. BP 220/150 mmHg. Urinalysis shows 4+ proteinuria, +hemoglobinuria, but no RBCs. Elevated creatinine.

What does the PB smear reveal (ignore arrows) about the BM function in this patient?

Back 83

Erythroid compartment is responsive to a hemolytic insult (presence of reticulocytes)

Front 84

Case 3: 42 yo AA male presents w/ headaches and altered mental status. PMH shows end-stage kidney disease secondary to long-standing HTN. BP 220/150 mmHg. Urinalysis shows 4+ proteinuria, +hemoglobinuria, but no RBCs. Elevated creatinine. PB smear shows schistocytes / fragments and reticulocytes.

The most likely diagnosis to explain the patient's symptoms and lab findings are?

Back 84

Malignant HTN

Front 85

Case 3: 42 yo AA male presents w/ headaches and altered mental status. PMH shows end-stage kidney disease secondary to long-standing HTN. BP 220/150 mmHg. Urinalysis shows 4+ proteinuria, +hemoglobinuria, but no RBCs. Elevated creatinine. PB smear shows schistocytes / fragments and reticulocytes.

All of these patients may present with similar PB findings, except?

Back 85

5 yo w/ splenic sequestration would not present with schistocytes and reticulocytes

Front 86

Case 3: 42 yo AA male presents w/ headaches and altered mental status. PMH shows end-stage kidney disease secondary to long-standing HTN. BP 220/150 mmHg. Urinalysis shows 4+ proteinuria, +hemoglobinuria, but no RBCs. Elevated creatinine. PB smear shows schistocytes / fragments.

The pathophysiology of this patient's disease is best characterized as?

Back 86

RBC fragmentation disorder

Front 87

What can cause mechanical trauma to RBCs?

Back 87

- Extreme heat / burn
- Defective cardiac valves
- Microangiopathic hemolytic anemias

Front 88

What are the disorders that can cause Microangiopathic Hemolytic Anemias?

Back 88

- Thrombotic Thrombocytopenic Purpura (TTP)
- Malignant HTN
- Anti-phospholipid Ab Syndrome
- Disseminated Intravascular Coagulation (DIC)
- Disseminated cancer

Front 89

What happens to the vessels in malignant HTN? Implications for RBCs?

Back 89

Hyaline Atherosclerosis - shears RBCs d/t thickening

Front 90

What happens to the vessels in Thrombotic Thrombocytopenic Purpura? Implications for RBCs?

Back 90

- Fibrin clots occlude RBC transport
- Leads to shearing of RBCs into fragments

Front 91

What disorder is caused by an acquired mutation in the PIGA gene?

Back 91

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Front 92

What happens in Paroxysmal Nocturnal Hemoglobinuria (PNH)? Cause?

Back 92

- Rare disorder
- Acquired mutation in PIGA gene on X chromosome
- Results in decreased GPI-linked proteins

Front 93

What are the implications of the PIGA gene mutation in Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Back 93

- Lack of GPI-linked anti-complement proteins makes cells susceptible to complement lysis
- All myeloid lineages are affected, though RBCs are most sensitive to complement lysis

Front 94

What is the clinical presentation of Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Back 94

- Chronic low level hemolysis
- Acute, episodic hemolysis events
- Hemoglobinuria
- Venous thromboses

Front 95

How do you diagnose Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Back 95

Flow Cytometry for GPI-linked proteins
PNH if there is a deficiency of:
- CD55 (DAF)
- CD59
- Examined on WBCs and RBCs