Catch up in hematology

May the force be with you

Topic• Anemia

• Cytopenia

• VTE

• Bleeding disorder

• Hematologic malignancy

Anemia

Anemia by WHO

• Male Hb < 13 g/dL

• Female Hb < 12 g/dL (event in menopause)

• Pregnancy Hb < 11 g/dL

Clinical approach• Acute anemia

• Symptomatic

• Sudden onset

• Usually bleeding or hemolysis

• Precipitate by infection/drugs/trauma

Clinical approach

• Chronic anemia

• Usually asymptomatic/mild symptom (considering very low Hb)

• Usually decrease production (marrow/nutrition)

Iron def• Low MCV High RDW

• Reproductive age female

• Low T sat, Low SI, High TIBC, low ferritin

• Ferrous sulfate 1x3 at maximum (< 200mg/day)

• Further iron supplement 6-9 months

Thalassemia• Genetic disease

• Alpha gene chromosome 16

• Beta gene chromosome 11

• Transfusion dependent vs NTDT

• CBC show low MCV high RDW

• Enlarged spleen

Hb typing• ↓Hct ↓Hb ↓MCV ↑RDW

• A2 > 3.5% Beta trait

• A2 25-35% = E trait

• E > 85% = HomoE (very mild or no anemia)

• H = H disease

• CS 5-6% = Homo CS disease

Hb tying

• A2 10-25% = E trait with alpha-thal or IDA

• E ≅F = E/beta-thal

• A E Bart = AE Bart’s disease (HbH with E trait)

• E F Bart = EF Bart’s disease (HbH with Homo E)

Complication• Hemochromatosis

• NTDT ferritin > 800 ng/mL start chelation

• TD ferritin > 1,000 ng/mL start chelation

• Assessment

• Cardiac and liver MRI T2*

• Liver Bx

Chelation• Deferoxamine SC continuous injection

• Ototoxicity, visual disturb bancla

• Deferasirox Oral Once a day

• Deferiprone Oral 3-4 times a day

• Malaise, N/V, joint pain

Complication

• Extramedullary hematopoiesis

• Ix MRI

• Tx RT, transfusion, hydroxyurea

Complication

• Megaloblastic crisis

• Hemolytic crisis

G-6-PD def.• Male predominant (X-link gene)/Lionization in

female

• WHO type 3 (10-60% with stress induced lysis)

• Precipitated by oxidative stress (sulfa, etc.)

• Normal or mildly increased MCV(∵polychromatia)

• Resolve in 7-10 days

Hereditary Spherocytosis

• AD inherit

• Mild splenomegaly

• May complicated by gall stone

• normal MCV with High MCHC

• Definite treatment is splenectomy

Megaloblastic anemia• Folate or B12 def

• Folate

• Increase homocysteine

• B12

• Increase MMA (methylmalonic acid)

• Increase homocysteine

Megaloblastic anemia• MCV 110-120 High RDW (>130 =auto-agglutination)

• In B12 def

• Hair greying, beefy tongue, impair proprioceptive, dementia

• Mild jaundice, mild fever, mild pancytopenia

• Hypersegmented neutrophil (5-lobe 5%, 6-lobe 1%)

Pernicious anemia

• B12 def from impaired absorption

• Ab to parietal cells or intrinsic factor

• Associated with CA stomach

• Associated with autoimmune including thyroiditis, vitiligo, etc

Pernicious anemia• Treatment

• Cyanocobalamine 100 mcg SC

• OD x 1 wk

• weekly x 1 month

• Then monthly life-long

• Always replace B12 before folate

AIHA• Direct Coomb test positive

• IgG (warm), C3d (cold)

• Gradual onset of anemia and jaundice

• Look for other autoimmune disease, lymphoma

• Tx Prednisone 1 mkd, IVIg, rituximab

• splenectomy is work for warm type

Cytopenia

Thrombocytopenia• Drug induced

• Immune onset 7-10 days (ATB)

• Myelosuppression onset several weeks (rifam, depakene)

• ITP

• TTP/HUS

• DIC

ITP• Plt < 100,000/mcL without cause

• Acute < 3 months

• Persistent 3-12 months

• Chronic > 12 months (Keep Plt > 30,000)

• Look for associated autoimmune

• Treatment Pred 1 mkd, Dexa 40 mgx4days, IVIg, Anti-D, rituximab, splenectomy

TTP/HUS• Pentad (fluctuate neuro, fever, MAHA, low Plt, AKI)

• Rarely bleed

• Low ADAMTS13 (<10%)

• Platelet transfusion is contraindication if no bleed

• Plasma exchange, prednisone, plasma infusion

• Look for HIV, drug (Ticlopidine)

DIC• MAHA + low platelet + coagulopathy + D-dimer > 500

ng/mL

• Acute form severe tissue injury (severe sepsis, large trauma, abruptio placenta, etc.)

• Chronic form (Kassabach-Merit, Trousseau syndrome)

• Treat cause, transfusion only if bleeding

• Heparin in presence of thrombosis

Neutropenia• Febrile neutropenia

• Fever 38.3 or 38 x 1 hr

• Neutropenia ANC < 500 or < 1,000 and decreasing

• If relatively lymphocyte predominate indicate marrow cause

• Drug induced onset several weeks (antipsychotic)

Aplastic anemia• Pancytopenia with hypocellular marrow <25%

• Severe AA: marrow cellularity (2 of 3)

• Reticulocyte count < 60,000

• Platelet < 25,000

• ANC < 500

• Vert severy < 250

Aplastic anemia• Look for drugs, flowcytometry for PNH (CD55,59)

• Severe and very severe

• AlloSCT

• Antithymocyte immunoglobulin + CSA

• Non-severe

• Androgen

VTE

VTE• Provoked VTE

• Hormone, surgery, inflammation, CA, APS

• Non-provoked VTE

• Genetic predisposing -> family Hx

• Protein C,S deficiency, factor V Leiden, protrombin 20210

VTE Treatment• Heparin overlap(5 days at least) with warfarin keep

INR 2-3

• NOAC

• Rivaroxaban

• Apixaban

• LMWH overlap with dabigatran

VTE Treatment• Duration

• Provoked: 3 months

• Unprovoked: 3 months then consider risk of bleeding (~1%/y) vs recurrent (10,20,30,40% at 1,3,5,10 years)

• APS: life long

• Recurrent: life long

Diagnosis of APS

Diagnosis of APS• Objective confirm vascular thrombosis

• Pregnancy-related morbidity

• 3 abort in <10 wk or

• 1 abort after 10 wk or

• Preterm < 34 wk ∵eclampsia/severe preeclampsia of placental insufficiency

Diagnosis of APS• One of these LAB +ve 2 or more at least 12 wk

apart

• Lupus anticoagulant

• Anticardiolipin IgG/IgM* in moderate or high titre

• Anti-β-2GP1 IgG/IgM*

• >40 GPL or MPL or > 99th percentile

Bleeding disorder

Bleeding disorder• Congenital

• Hemophilia A,B

• vWD

• Acquired

• Warfarin overdose

• Acquired hemophilia (autoimmune)

Hemophilia A• X-link recessive

• Factor VIII level

• Mild 6-40%

• Moderate 1-5%

• Severe <1%

Hemophilia A• Treatment

• Give factor VIII/Cryoprecipitate/FFP as soon as trauma

• Dose = Desired level(%) x Wight(kg)

• 1 unit raise FVIII 2%

• Screening for FVIII Ab if frequent treatment

Hemophilia A• Example

• Male 70 kg with knee injury -> Desired level 60%

• Dose = 60% x 70 kg = 4200 ->

• FVIII 2100 units

• Cryoprecipitate 21 units

• FFP 2100 ml

FVIII Ab in hemophilia A• If < 5 Bethesda Unit -> give factor

• If > 5 Bethesda Unit -> give by passing agent

• FEIBA (aPCC)

• Prothrombinase complex concentrate

• rFVII cencentrate

Hemophilia B

• X-link recessive

• Approach similar to hemophilia A

• FIX 1 unit raise FIX 1%

• Cryoprecipitate does not contain FIX

von Willebrand Deficiency

• AD except type3

• Primary hemostatic

• Hemophilia-like in type3

• Late onset -> prolonged menstruation, tooth extraction, etc

vWD• vWF:Ag, vWF:Rco

• Type 1 decrease level

• Type 2 abnormal function

• Type 3 severe deficiency

vWD

• Treatment

• DDAVP for type1 0.3mcg/kg (max 20-24mcg)

• Cryoprecipitate 1 U/10 kg

• FVIII conc. that contain vWF (Rco unit) 40-60 U/kg

Hematologic Malignancy

Hematologic malignancy

• Acute leukemia

• Myeloproliferative neoplasm

• Lymphoproliferative disease

• Plasma cell dyscrasia

AML• Acute -> onset ~1 months

• Pancytopenia -> early disease “aleukemic leukemia

• Blast > 50,000 -> risk of leukostasis

• Monoblast > 30,000 -> of leukostasis

• Extramedullary disease=myeloid sarcoma/chloroma

AML• PBS show myeloblast with Auer’s rod

• Blast > 20% in marrow of peripheral blood

• Extramedullary disease=myeloid sarcoma/chloroma

• Prognosis depend on chromosome

• Good t(8;21), t(16;16)/inv(16)

• Intermediate t(9;11), normal

• Bad -5 -7 +8 complex, t(3;)/inv(3), t(6;9), t(v,11), -5, -7, abnl(17p)

Treatment• Hyperleukocytosis

• Leukapheresis + chemo (Hydrea or Ara-C)

• Induction (7+3) then consolidation of AlloSCT

• Supportive

• leukocyte reduced blood component

• TLS prevention

Tumor lysis syndrome• Hyper K+

• Hyper PO42-

• Hypo Ca2+

• Hyperuricemia

• Renal failure

• Anuria

Tumor lysis syndrome• Hydration

• ± alkalinized urine

• Allopurinol

• Rasburicase

• Dialysis

ALL/lymphoblastic leukemia

• Similar to AML

• Younger age group

• May have lymphadenopathy and hepatosplenomegaly

• Prognosis depend on chromosome, age, T or B cell

• Induction/consolidation/maintenance or AlloSCT

MDS• Anemia or bi- or pancytopenia

• Dysplastic change

• Pseudo Pelger-Huët anomaly

• Megaloblastoid change in marrow

• Prognosis depend on chromosome/blast/cytopenia

MPN• Philadelphia chromosome +ve MPN

• CML

• Philadelphia chromosome -ve MPN

• PV

• ET

• PMF

CML• Philadelphia chromosome -> t(9;22)

• Usually asymptomatic

• High WBC with all stage of myeloid cell

• mild or no anemia and high platelet

• Panmyelosis marrow with dwarf megakaryocyte

CML• Chronic phase

• Treat with TKI (imatinib,nilotinib,dasatinib)

• Accelerated phase

• Blastic phase -> blast > 20% in blood or marrow or cluster of blast in marrow or myeloid sarcoma

• AlloSCT in blastic phase or TKI failure

Polycythemia vera• Hb > 18.5 g/dL in male, 16.5 in female

• Usually have high WBC and Plt

• JAK2V617F mutation in 95% (exon 12 mutation in the rest)

• Rule out secondary cause

• Can progress to myelofibrosis or AML

Polycythemia vera• Tefferi criteria

• Age ≥ 67 (5) 57-66 (2)

• WBC ≥ 15,000 (1)

• Hx of vascular event (1)

• 4:high, 3:int-2, 1-2:int-1, 0:low

• ASA for all, cytoreductive of high risk, phlebolectomy for Hct > 45%

Essential thrombocythemia

• Plt > 450,000 for 6 months

• JAK2V617F in 50% of case

• Increased large hyperlobated bizarre shape megakaryocyte

• Small chance of MF or AML

Essential thrombocythemia• IPSET-thrombosis

• Age ≥ 60 (1)

• Hx of vascular event (2)

• CVD risk (1) (DM, HT, smoking)

• JAK2V617F (2)

• 3:high, 2:int, 1:low

• Low: ± ASA, Int or more: ASA + cytoreductive

Primary myelofibrosis• Pancytopenia with enlarged spleen

• Leukoerythroblastic blood picture

• Progress into AML

• Treatment

• supportive in low risk

• AlloSCT in high risk and fit

• Ruxolitinib can reduce spleen size and improve survival

Lymphoproliferative disease

• Aggressive

• DLBCL, Hodgkin, mantle cell lymphoma, Burkitt lymphoma, TCL

• Indolent lymphoma

• Follicular lymphoma, CLL/SLL, MALT lymphoma

Lymphoproliferative disease• Aggressive

• Progress in several weeks or months

• Need systemic chemotherapy

• Indolent

• Progress over many years

• Local treatment

• In advance stage need treatment only if symptomatic

Hodgkin lymphoma

• Bimodal age distribution (20 and 60 year)

• Alcohol precipitates pain in the node

• Very good prognosis

• In HIV usually occurs in higher CD4 (150-250)

DLBCL• Large cell with CD20+

• IPSS score

• Age > 60

• ECOG > 2

• Stage III-IV

• Extranodal involvement (spleen is nodal)

• Elevated LDH

Plasma cell dyscrasia• MGUS

• M-protein < 3 g, marrow plasma cell < 10%

• Smoldering MM

• M-potein > 3 g, marrow plasma cell > 10%

• MM

• With CRAB

Plasma cell dyscrasia• CRAB

• Calcium > 11 g/dL

• Renal insuff (creatinine > 2 mg/dL)

• Anemia (Hb < 10 g/dL)

• Bone lytic lesion

Plasma cell dyscrasia

• Age ≤ 65 year -> transplant eligible

• Novel agent + chemo + steroid (avoid alkylating angent)

• Age > 65 year -> transplant ineligible

• Melphalan + novel agent + steroid

Amyloidosis

• Amyloid light chain

• Apple green in Congo Red

• Renal involvement cause proteinuria

• Cardiac involvement cause increased Trop-T

Good luck!