Anemias due to RBC destruction or loss

hemolytic anemia definition

-premature destruction of RBC (<120 days)

-caused by hemolysis

hemolytic anemia classification

intrinsic defect: abnormality with RBC itself

extrinsic defects: normal RBC destroyed by external factors

hemolytic anemia clinical manifestation

signs that suggest hemolysis

-jaundice/scleral icterus

-dark urine (intravascular)

-splenomegaly (extravascular)

hemolytic anemia common diagnosis

CBC- low H/H

RI- elevated

bilirubin- elevated

haptoglobin- decreased

LDH- elevated

DAT

hemolytic anemia common treatment

-folic acid supplementation

-RBC transfusion

-iron chelation

-other thing specific to disease

hemolytic anemia common complications

-iron overload

-gallstone of bilirubin

-folate deficiency

-hemolytic crisis (ton RBC erupt)

-aplastic crisis

inherited hemolytic anemias

-Hereditary spherocytosis

-Hereditary elliptocytosis

-G6PD deficiency

-Pyruvate kinase deficienc

hereditary spherocytosis epidemiology

-intrinsic hemolytic anemia

-most common RBC membrane disorder

-autosomal dominant inheritance

hereditary spherocytosis pathophysiology

-genetic mutation > defect in RBC membrane proteins > loss of membrane surface area > produced spherical RBC > spherocytes trapped and destroyed in spleen

hereditary spherocytosis risk factors

-family history

-physiological stressors: pregnancy, infection, surgery can lead to hemolytic crisis

hereditary spherocytosis symptoms

-varies from asymptomatic to severe

-basic anemia symptoms

-hemolytic symptoms: jaundice

-hemolytic/aplastic crisis with parvovirus B19 infection

hereditary spherocytosis signs

-vital sign abnormalities if severe

-pallor

-jaundice/icterus

-splenomegaly

-right upper quadrant pain if gallstones

hereditary spherocytosis diagnosis

CBC:

MCHC: elevated

Reticulocyte count: elevated

PBC: spherocytes

DAT: distinguish from hemolytic anemia osmotic fragility test

hereditary spherocytosis treatment

avoid oxidative stressor

-splenectomy

-vaccination key in asplenic patients

-daily folic acid supplementation

-transfusion as needed

hereditary elliptocytosis epidemiology

-more common in malaria epidemic regions

-autosomal dominant inheritance

-most mild or asymptomatic

hereditary elliptocytosis pathophysiology

genetic mutation > defect in spectrin protein used to make RBC skeleton > abnormal skeleton leds to elliptical/elongated RBC shape > variable degree of hemolysis

hereditary elliptocytosis etiology

-genetic mutation

- alpha-spectrin (SPTA1) most common

hereditary elliptocytosis risk factors

-family history

-physiologic stressors

hereditary elliptocytosis symptoms

-most patients are asymptomatic or have mild anemia

Severe forms present with:

-anemia symtpoms

-hemolytic symptoms

hereditary elliptocytosis signs

-normal in mild cases

Severe cases:

-vital signs abnormal

-pallor

-jaundice

-splenomegaly

hereditary elliptocytosis diagnosis

CBC: normal

Reticulocyte count: normal or +

PBS: >25% elliptocytes (cigar shape)

Direct coombs: negative

hereditary elliptocytosis treatment

-observation from most cases

-severe: mitapivat

G6DP deficiency epidemiology

-most common deficiency worldwide

-x linked recessive inheritance

-africa

G6DP deficiency pathophysiology

-G6PD: produces NADPH

-NADPH protects RBC from damage

genetic defect of G6PD > less NADPH > cant neutralize oxidative stress > RBC membrane damage > intravascular and extravascular hemolysis during time of oxidative stress

G6DP deficiency etiology

-genetic mutations in G6PD

-400 variants

G6DP deficiency risk factors

-males

-african

Exposure oxidative stress:

-sulfonamides, nitrofurantoin, vitamin K, diphenhydramine,

isoniazid, acetaminophen

-fava beans

-infections

G6DP deficiency symptoms

-most patients chronic compensated hemolytic anemia with episodic acute hemolysis

-triggered by hemolytic stress

-signs of anemia

-hemolysis: dark urine, jaundice, pain

G6DP deficiency signs

usually catching during hemolytic episode: jaundice, mild splenomegaly, dark urine

G6DP deficiency diagnosis

-most appear normal when not in acute phase

-PBS: bite cells, heinz bodies

-Urinalysis: hemoglobinuria

-G6DP enzyme activity assay: tests patients levels = low

G6DP deficiency treatment

-removal/avoid triggering stressors

-supportive care

-severe= transfusion

pyruvate kinase deficiency epidemiology

-autosomal recessive inheritance

pyruvate kinase deficiency pathophysiology

genetic mutation in PKLR gene > decreased pyruvate kinase activity > reduced ATP production > ATP depletion > impaired RBC membrane > RBC become rigid and dehydrated > RBC destruction in spleen (extravascular hemolysis)

pyruvate kinase deficiency etiology

-mutation in PKLR gene (chromosome 1q21)

-many mutations

pyruvate kinase deficiency risk factors

-family history

-parental consanguinity

-certain ethnic backgrounds

pyruvate kinase deficiency symptoms

-variable

-hemolysis is chronic

-anemia symptoms

-hemolysis symptoms fluctuate

pyruvate kinase deficiency signs

-can be normal

-pallor, jaundice, splenomegaly

-frontal bossing in severe cases (children more prominent)

pyruvate kinase deficiency diagnosis

CBC: normal

reticulocyte count: elevated

PBS: Burr cells, acanthocytes

hemolysis marker: elevated

DAT: negative

PK enzyme activity assay: test PK enzyme = reduced

pyruvate kinase deficiency treatment

-avoid oxidative stressors

-depends on severity

-monitoring

-folic acid supplement

acquired hemolytic anemias

-Paroxysmal nocturnal hemoglobinuria (intrinsic)

-Autoimmune hemolytic anemia (extrinsic)

-Microangiopathic hemolytic anemia (extrinsic)

Paroxysmal nocturnal hemoglobinuria epidemiology

-rare acquired clonal hematopoietic stem cell disorder

-30-40 years

-association with bone marrow failure

Paroxysmal nocturnal hemoglobinuria pathophysiology

acquired mutation in PIG-A gene B > abnormal sensitivity of RBC membrane to lysis by complement > intravascular hemolysis

-acquired mutation will also come from thrombosis, bone marrow failure

Paroxysmal nocturnal hemoglobinuria etiology

-acquired somatic mutation in PIG-A gene

-immune mediated bone marrow injury

Paroxysmal nocturnal hemoglobinuria risk factors

-history of anemia or bone marrow failure

-immune disorders

-immunosuppressive therapy

Paroxysmal nocturnal hemoglobinuria symptoms

-anemia symptoms

-hemolysis symptoms: dark urine in morning

-thrombosis

Paroxysmal nocturnal hemoglobinuria signs

-pallor, jaundice

-thrombosis

-petechiae, purpura id thrombocytopenia

Paroxysmal nocturnal hemoglobinuria diagnosis

CBC: normal

reticulocyte count: elevated

PBS: nonspecific

hemolysis marker: elevated LDH

Urinalysis: Hemoglobinuria

DAT: negative

FLOW Cytometry: gold standard

Paroxysmal nocturnal hemoglobinuria treatment

-folic acid supplement

-transfusion

stem cell transplant only curative option

-anticoagulation for thrombosis

Paroxysmal nocturnal hemoglobinuria education/prognosis

thrombosis is main cause of mortality

Autoimmune Hemolytic Anemia (AIHA) epidemiology

-extrinsic

-warm AIHA: more common female

-cold AIHA: when they are colder

Autoimmune Hemolytic Anemia (AIHA) pathophysiology warm

IgG auto auto-antibodies bind to RBC membrane > RBC undergo extravascular hemolysis within the spleen

Autoimmune Hemolytic Anemia (AIHA) pathophysiology cold

IgM auto-antibodies bind to RBC at low temp > complement activation > intravascular hemolysis of RBC

Autoimmune Hemolytic Anemia (AIHA) etiology

-primary idiopathic 50%

-secondary: other autoimmune disorders

Autoimmune Hemolytic Anemia (AIHA) risk factor

-autoimmune disorder

-older

-female

-cold exposure

Autoimmune Hemolytic Anemia (AIHA) symptoms warm

-gradual onset of anemia and hemolysis symptoms

Autoimmune Hemolytic Anemia (AIHA) symptoms cold

-similar to warm but worsen when cold

-acrocyanosis

-hemoglobinuria after exposure

Autoimmune Hemolytic Anemia (AIHA) signs

warm- splenomegaly

cold- acrocyanosis

-other classic symptoms for both

Autoimmune Hemolytic Anemia (AIHA) diagnosis

CBC: normal

reticulocyte count: elevated

PBS: spherocytes, polychromasia

RBC agglutination in cold AIHA

DAT: positive

Autoimmune Hemolytic Anemia (AIHA) treatment

-treat underlying condition

-warm: corticosteroids (prednisone 1-2mg/kg/day)

-cold: avoid cold, DMARDS (Rituximab)

Microangiopathic Hemolytic Anemia epidemiology

-extrinsic

-RBC damage by circulation then lysis

Microangiopathic Hemolytic Anemia pathophysiology

RBC in perpherial blood due to trauma > damaged/activated endotherlium > platelet adhesion/thrombi > intravascular hemolysis of RBC, form clots

Microangiopathic Hemolytic Anemia etiology

many

-TTP, HUS, DIC

-anything that causes direct mechanical damage to RBC

Microangiopathic Hemolytic Anemia risk factors

-underlying cause

Microangiopathic Hemolytic Anemia symptoms

-acute onset of anemia and hemolysis symptoms

- features of underlying cause

Microangiopathic Hemolytic Anemia signs

-pallor, jaundice

-dark urine, petechiae, purpura

-specific to underlying cause

Microangiopathic Hemolytic Anemia diagnosis

CBC: normal

reticulocyte count: elevated

PBS: schistocytes >1%

hemolysis marker: elevated LDH

DAT: negative

Microangiopathic Hemolytic Anemia treatment

-management of underlying cause

-supportive care

hemorrhagic anemia

caused by acute blood loss

-treatment aimed to stop hemorrhage

Acute Posthemorrhagic Anemia (APHA) Epidemiology

-common from due to acute blood loss

-trama is leading cause

-GI bleeding

Acute Posthemorrhagic Anemia (APHA) pathophysiology

some sort of trauma that leads to bleeding > acute blood loss leads to anemia

-hypovolemia (min to hr)

- conversion to anemia (hr to day)

-bone marrow responds (days to weeks)

Acute Posthemorrhagic Anemia (APHA) etiology

-some form of acute blood loss

-external bleeding: trauma

-internal bleeding: HI, OB

Acute Posthemorrhagic Anemia (APHA) risk factors

-trauma

-antiplatelet meds

-GI

-OB

Acute Posthemorrhagic Anemia (APHA) symptoms

-symptoms depend on rate of blood loss

-mild <15% minimal symptoms

-moderate 15-30% tachy, hypotension, weak

-severe 30-40% tachy, hypotension, confusion

-critical >40% shock

Acute Posthemorrhagic Anemia (APHA) diagnosis

initially: CBC and reticulocyte count =normal

Type and screen in preparation for transfusion

Acute Posthemorrhagic Anemia (APHA) treatment

-control bleeding

-IV fluids

-transfusion