Benign hematology facts Flashcards by Erez Halperin

Definition of Transfusion independence in thalassemia

less than 6 PC in 6 months
no PC in previous 2 months

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Hb in Thalassemia intermedia

7-10 g%

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Beta thalassemia intermedia genotype

Compound heterozygotes

Homozygotic to non severe mutations (b0/b+)
# Beta heterozygote with alpha gene excess
# Hemoglobin E/β-thalassemia

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Hereditary spherocytosis inheritance

AD 66%

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Disease more common in NTDT

PHTN including RV dys
VTE
Silent cerebral ischemia
Cholelithiaisis
Leg ulcer
Splenomegaly

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Luspa for NTDT

BEYOND study
improves Hb levels after 3 months
Decreases ferritin

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Indications for iron chelation in NTDT

Ferritin level > 800 ng/mL
Liver iron concentration > 5 mg/g

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Hydrea in NTDT

Improves Hb (1 g%)
May aid with PHTN/Extramedullary hematopoiesis

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Reasons to start transfusions in NTDT

PHTN
Extramedullary hematopoiesis
Worsening anemia

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Deferasirox in NTDT

PO
THALASSA trial
Improved iron overload in NTDT
Approved also for TDT
SE: GI, rash, LFT, increased Cre, loss of hearing, cataract
New formulation JADENU with less SE. Not approved in Israel

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Dose related drug neutropenia vs. agranulocytosis

Mild neutropenia is dose dependent- usually asymptomatic
Agranulocytosis is immune mediated and usually pts are febrile

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Mortality rates in agranulocytosis

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Ferrinject in HF pts with IDA

HEART-FID trial
Phase III
vs placebo
Did not show benefit in composite outcome
Results might have been affected by covid

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Hereditary spherocytosis gene

ANK1
Band3
Spectrin
Protein 4.2

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Hereditary spherocytosis prevalence

1/1000

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HS special hemolytic complications

Neonatal jaundice
Megaloblastic crisis- due to folate def during pregnancy

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Iron overload parameters in HS

Ferritin >500 mg/l
Saturation >60%
Liver iron concentration >4

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Renal complications of HS

Distal renal tubular acidosis
in Band3 mutated pts

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HS diagnosis

Screen-
# EMA- reduced binding of EMA to band 3 (more sensitive and specific)
# Osmotic fragility

Confirm- Genetic testing

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Contraindication for splenectomy in hereditary hemolytic anemias

Dehydrated hereditary stomatocytosis
Due to high thrombotic risk

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Stomatocytosis

Light wide transverse band in the middle of erythrocytes (stoma)
PIEZO1 in dehydrated

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Acquired stomatocytosis

Alcoholism
Hepatobiliary disease
Malignant neoplasms
CV disorders

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Rapidly progressive hemolytic
anemia in alcoholism

Zieve syndrome
Association with end-stage alcoholic cirrhosis
Acanthocytes are present

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McLeod phenotype

Acanthocytes due to reduced kell antigen
X linked
Causes hemolysis

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Rh deficiency (null) syndrome

Full or partial lack of Rh causing mild hemolysis

Diagnostic test for congenital enzymopathies and skeletal RBC abnormalities

Targeted NGS

Coombs negative AIHA %

10%

Secondary warm AIHA etiologies (5 causes)

1. LY (CLL) 2. AI (SLE) 3. Non lymphoid cancers (ovarian tumors) 4. Inflammatory diseases (UC) 5. Drugs (Cephalosporins, NSAIDs, Fludarabine)

Secondary CAD etiologies

1. Postinfectious (Mycoplasma pneumoniae/EBV) 2. LY 3. AI

PCH etiology

Primary Viral (pediatric) Syphilis

IgM target in CAD

I Antigen (mycoplasma) i Antigen (EBV)- does not exist in adults

IgG target in PCH

P Antigen

Rituximab benefit in warm AIHA

Increases response rates 75% vs 30% in 1 year

Agents with activity as 2nd/3rd line in warm AIHA

MMF Azathioprine CY CsA Danazol Bortezomib

Tapering doses in AIHA

Start tapering after 2-3 weeks 20 mg at 2 months Discontinuation not before 6 months

Agents with activity in CAD

Bendamustine Bortezomib Ibrutunib Sutimlimab

Drug induced TMA agents

Plavix Mitomycin Gemcitabine Tacrolimus Sirolimus Quinine Emicizumab High doses of FEIBA

Tx of Shiga toxin associated TMA

Eculizumab seems promising

Agents causing direct damage to RBCs- resulting in hemolysis

Copper/Lead Dapsone/Sedural/Ribavirin Snake/Spider bites Burns

HbA2 levels diagnostic of b-thalasemia

>3.5%

TD beta thalassemia genotype

b0/b0 Severe HbE/b-thalassemia syndromes

NTDT syndromes

b-thalassemia intermedia Moderate HbE/b-thalassemia syndromes

a-thalassemia silent carrier genotype

-a/aa

a-thalassemia trait genotype

--/aa -a/-a

HbH genotype

--/-a b4 tetramer

TDT alpha thalassemia genotype

Severe types of HbH

NTDT alpha thalassemia genotype

Mild-moderate types of HbH

Hb electrophoresis in alpha thalassemia

Trait and silent carrier- normal NTDT and TDT- 5-40% of HbH

Chelation goal in TDT

Ferritin of <1000 ng/mL LIC of <5 Cardiac T2* of >20 ms

Deferoxamine

Tx of TDT thalassemia SC or IV infusion Continous infusion SE: FTT, loss of hearing, retinopathy, yersinia infections, OP

Deferiprone

Tx of TDT thalassemia PO SE: agranulocytosis!, GI, LFT, arthralgia, zinc deficiency

Luspatercept for TDT

BELEIVE Reduction in transfusion of 33% Increased VTE

SCD genotype

HbSS, HbSb0- severe (causing anemia) HbSC, HbSb+-mild

Sickle cell trait complications

Splenic infarction at high altitude Hematuria Renal papillary necrosis Pyelonephritis during pregnancy Medullary carcinoma of kidney VTE | SHARP MV ## Footnote pointy like the cells dead

Effect of a-thalassemia on SCD

Reduces hemolysis and risk of VTE

Haplotype of S in SCD with worst prognosis

Central African Republic (CAR) | worsens when cold

Differentiating HbSS and HbSB0

MCV

Acute chest syndrome Sx

Similar to pneumonia

Risk factors of developing acute chest syndrome

Young age, male Low HbF High WBC High steady state HbS

Leading cause of death in SCD

Acute chest syndrome

Exchange transfusion indication in SCD with acute chest syndrome

Hypoxemia despite oxygen Widespread infiltrates, Rapid clinical deterioration.

Preventive measures for acute chest syndrome in SCD

HU Chronic RBC transfusions

Silent cerebral infarcts in SCD %

30% children 50% adults

Disease modifying Tx in SCD

HU L-glutamine Crizanlizumab (anti p-selectin) Voxelotor (HbS polymerization inhibitor)

Benefit of HU in SCD

Reduces pain episodes, acute chest syndrome, and transfusions

L-glutamine benefit in SCD

Reduces pain crisis in addition to HU

HbE

Trait- Asymptomtic Homozygotes- mild microcytic anemia

HbC

HbCC or HbC beta-thalssemia have mild anemia with splenomegaly

Gaucher disease clinical manifestations

Hepatosplenomegaly Cytopenias Bone deformation and pain

Gaucher disease diagnosis

Decreased glucocerebrosidase activity Genetic

Gaucher disease Tx

Enzyme replacement therapy

Incidence AIHA

2/100K

Mortality AIHA

FP coombs causes

Allo Ab- 3 months from transfusion Dara IVIG Sepsis- non specific Ab due to increased Ab in plasma

Primary vs secondary AIHA %

50%-50%

Which IgGs are clinically important for hemolysis

IgG1 IgG3

Severe wAIHA necessitating rituximab

Hb <8 Transfusion Evans IgA

Novel Tx in AIHA

Protesome inhibitors CD38 i Fosfamatinib BTKi

Nipocalimab

Anti FcRn Prevention of fetal hemolysis Novel Tx of wAIHA with combination with PEX

Cold agglutination titer

1/64

Monoclonal in CAD %

80% IgMk

Complement inhibition in CAD

Sutimlimab C1 inhibitor In acute hemolysis Bridging Tx to rituximab

Alpha globin chromosome

Beta globin chromosome

Hb goal in thalassemia

Luspa SE

Bone pain Extramedullary hematopoesis- consider imaging prior to Tx in thalassemia May be teratogenic Thrombosis Fatigue GI

HbS goal of exchange transfusion in SCD

HbS> 40%

Cold agglutinin titer for CAD

1st line Tx of choice for CAD

BR X4 60% CR with long DoCR Time to best response is long (6-7 months) R alone is also an option

Indications for BMB for mild anemia

Macrocytosis Other cytopenias FHx Dysplasia on PB

B12 deficiency definition

B12<200 or B12 < 300 and MMA > ULN

Target Ferritin in CKD pts

300-500

HbSC / HbSβ+ vs HbSS phenotype

Higher Hb with fewer complications May be diagnosed in older age

Tx of splenic squestraion in SCD

Transfusion

Tx indication in CAD

Only if Sx Cold avoidance is reccomended for all

IV iron indications

CKD CHF Cancer Poor abdorption Urgent needs

Common drugs causing drug induced AIHA

Cephalosporins, NSAIDs, PD1