Bleeding Disorders - banponghospital · Bleeding Disorders Clinical Features Platelet Disorders...

Chapter III D45-D89 Diseases of the blood and

blood-forming organs

นพ.บก เจญล

กมงานลยกรรม รพ.สวรรประชาก นครสวรร

1

Bleeding DisordersBlood Vessel

constriction

Platelet Aggregation

Coagulation Cascade

Blood Vessel Disorders Platelet Disorders Coagulation Disorders

Hereditary

- Telangiectasia

- Marfan syndrome

Function disorder

- Drug: aspirin, clopidogrel

- Renal failure

Hereditary

- Hemophilia

- von Willebrand’s disease

Acquired

- Aging

- Scurvy

- Drug: steroids

- Viral infection

Thrombocytopenia

- Immune: ITP

- Viral infection

- Aplastic anemia

- Chemotherapy

- Blood transfusion

Acquired

- Liver disease

- Drug: heparin

- Immune

- Blood transfusion

Disseminated Intravascular Coagulation: All factor deficiency

2

Bleeding Disorders

Clinical Features Platelet Disorders Coagulation Disorders

Site of beeding Skin

Mucous membranes

Deep in soft tissue (Joints,

Muscles)

Petechiae Present Absent

Ecchymosis (Bruises) Small, superficial Large, deep

Hemarthrosis Extremely rare Common

Bleeding after cuts &

scratches

Yes No

Bleeding after surgery or

trauma

Immediate, usually mild Delayed 1-2 d often severe

3

Thrombocytopenia

Thrombocytosis

Platelet Dysfunction

Platelet Disorders

4

Thrombocytopenia

Decreased Production Increased Destruction Abnormal Distribution

Marrow damage Aplasia

Drugs/Toxins

Hepatitis

Malignancy

Congenital defects Fanconi anemia

TAR syndrome

Rubella

Wiskott-Aldrich syndrome

Autosomal dominants

Ineffective production B12/Folate deficiency

Non-immune DIC

Hemolytic-uremic syndrome

TTP

HELLP syndrome

Immune Drug-induced

Secondary to

SLE

AIDs

Alloimmunization

ITP

Splenomegaly Liver disease

Myelofibrosis

Dilution Multiple blood transfusion

Kasabach-Merrit syndrome

5

5

TTP Schistocytes, Hemolysis (incr. TB/DB, LDH, low

haptoglobin), Thrombocytopenia, Fever, Renal, CNS,

Normal PT & Normal PTT

HUS Schistocytes, Hemolysis (incr. TB/DB, LDH, low

haptoglobin), Thrombocytopenia, Fever, Renal, Normal

PT & Normal PTT but no CNS

DIC Schistocytes, Hemolysis (incr. TB/DB, LDH, low

haptoglobin), Thrombocytopenia, Fever, Renal, &

Bleeding but Elevated PT & PTT

Evans’ syndrome Autimmune Hemolysis (positive Coomb’s test) &

Autoimmune Thrombocytopenia [Others - normal]

ITP Autimmune Thrombocytopenia with no systemic

disease [Others - normal]

Thrombocytopenia

6

Hypersplenism

A disorder which cause the spleen to rapidly and prematurely

destroy blood cells

Spleen will temporarily hold onto up to 90% of the body’s platelets

and 45% of the red blood cells

Splenomegaly

Anemia, Leukopenia and Thrombocytopenia [singly or

combination]

Normocellular or Hypercellular bone marrow

Decreased survival of RBC, Platelet

7

Drug Induced Immunologic Thrombocytopenia

Antibiotics, Hypnotics, Analgesics, Heavy metals, Diuretics,

Chloroquine, Digoxin, Heparin, Tolbutamide

Both the drug and antibody must be present in the system at

the same time for platelets destruction

Thrombocytopenia will occur after 12 hour of drug intake but

the time can still delayed

Thrombocytopenia mostly draws 5–7 day after discontinuation

Megakaryocyte in bone marrow is normal

8

Drug Induced Immunologic Thrombocytopenia

Antibiotics and Antivirals

• Quinine/Quinidine

• Penicillins

• Cephalosporins

• Vancomycin

• Trimethroprim/Sulfa.

• Sulfonamides

• Linezolid

• Valacyclovir

• Ganciclovir

• Indinavir

Cardiovascular medications

• Abciximab

• Tirofibran

• Epitifibatide

• Salicylates

• Digoxin

• Furosemide

Miscellaneous

• Ranitidine, Famotidine

• Valproate

• Interferon

9

Idiopathic Thrombocytopenic Purpura (ITP)

Thrombocytopenia occurs in the absence of any disease

associated with decrease platelet or toxin exposure

Acute ITP

2–6 years; after recovery from viral infection; self limiting

Chronic ITP

mostly 20–40 years women; rare remission

Neonatal ITP

transplacental passage of anti platelet antibody

10

Idiopathic Thrombocytopenic Purpura (ITP)

Thrombocytopenia occurs in the absence of any disease

associated with decrease platelet or toxin exposure

Acute ITP

2–6 years; after recovery from viral infection; self limiting

Chronic ITP

mostly 20–40 years women; rare remission

Neonatal ITP

transplacental passage of anti platelet antibody

11

Thrombocytopenia

Summary Diagnosis ICD-10

Primary thrombocytopenia

Hereditary thrombocytopenia

Fanconi anemia

Wiskott-Aldrich syndrome

Thrombocytopenia with absent radius [TAR]

D69.4

D69.4

D61.0

D82.0

Q87.2

Thrombocytopenia D69.6

Decreased Production

12

Thrombocytopenia


Disseminated intravascular coagulation [DIC]

Thrombotic thrombocytopenic purpura [TTP]

Idiopathic thrombocytopenic purpura [ITP]

Evans’ syndrome

Drugs-induced thrombocytopenia

Thrombocytopenia due to allimmunization

Hemolytic-uremic syndrome [HUS]

D65

M31.1

D69.3

D69.3

D69.5

D69.5

D59.2

Postpartum thrombocytopenia

HELLP syndrome

Transient neonatal thrombocytopenia

O72.3

O14.2

P61.0

Increased Destruction

13

Thrombocytopenia


Hypersplenism

Dilutional thrombocytopenia

Kassabach-Merrit syndrome

D73.1

D69.5

D69.5

Abnormal Distribution

14

Thrombocytosis

Platelet count >500,000 cells/mL

Etiology

• Reactive conditions to infection, inflammation, acute blood

loss, major surgery

• Iron deficiency

• Post splenectomy

• Essential thrombocythemia (ET)

15

Essential Thrombocythemia

A condition that the bone marrow overproduction of platelets,

leading propensity to thrombosis formation and blockage of vessels

Platelet count >600,000 cells/mL

Hematocrit <40% or normal RBC mass

Normal serum ferritin, or normal MCV

No Philadelphia chromosome or bcr/abl gene rearrangement

No cytologic or morphologic evidence of MDS

No cause for reactive thrombocytosis

16

Platelet Dysfunction

Congenital disorders Acquired abnormalities

von Willebrand’s disease

Glanzmann’s thrombasthenia

Bernard-Soulier syndrome

Myeloproliferative disease

Dysproteinemia

Cardiopulmonary bypass

Uremia

Liver disease

Drug inhibition

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Coagulopathy

Warfarin Adverse effect

Disseminated Intravascular Coagulation

Hemophilia

Coagulation Defect

18

CoagulopathyD68.3 Haemorrhagic disorder due to circulating anticoagulants

Haemorrhage during long-term use of anticoagulants

Hyperheparinaemia

Increase in:

· antithrombin

· anti-VIIIa

· anti-IXa

· anti-Xa

· anti-XIa

Use additional external cause code (Chapter XX), if desired, to

identify any administered anticoagulant

Excludes: long-term use of anticoagulants without

haemorrhage (Z92.1)

D68.4 Acquired coagulation factor deficiency

Deficiency of coagulation factor due to:

· liver disease

· vitamin K deficiency

Excludes: vitamin K deficiency of newborn ( P53 )

D68.5 Primary Thrombophilia-

-

-

-

D68.8 Other specified coagulation defects

D68.9 Coagulation defect, unspecified

D69 Purpura and other haemorrhagic

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Warfarin Adverse EffectDiagnosis Summary Diagnosis ICD-10

PDx Atrial fibrillation I48

CC Long-term use of warfarin Z92.1

EC

Diagnosis Summary Diagnosis ICD-10

PDx Prolonged PT due to warfarin use D68.4

CC

EC Y44.2

Diagnosis Summary Diagnosis ICD-10

PDx Epistaxis due to warfarin use R04.0

Cb D68.3

Cm Y44.2

น warfarin ตามแพทง

น warfarin ตามแพทง

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Prolonged prothrombin time (PT)

Thrombocytopenia

Elevated fibrin degradation product

Fragmented red blood cells

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Parameter Result Score

Platelet count (cells/ml)

>100,000 0

50,000-100,000 1

<50,000 2

Elevated fibrin-related markers

e.g. soluble fibrin monomers, fibrin

degradation products

no increase 0

moderate increase 2

strong increase 3

Prolonged prothrombin time

<3 seconds 0

3-5.9 seconds 1

>6 seconds 2

Fibrinogen level>1.0 g/L 0

<1.0 g/L 1

Total score >5 is

compatible with overt DIC

International Society of Thrombosis and Haemostasis

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ParameterAcute DIC

(decompensated)

Chronic DIC

(compensated)

Platelet count Reduced Variable

Prothrombin time Prolonged Normal

Partial thromboplastin time Prolonged Normal

Thrombin time Prolonged Normal

Plasma fibrinogen Reduced Normal/Elevated

Plasma factor V Reduced Normal

Plasma factor VIII Reduced Normal

Fibrin degradation products Elevated Elevated

D-dimer Elevated Elevated

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Disseminated intravascular coagulation

Neonatal DIC

D65

P60

Abruptio placenta with DIC

Antepartum hemorrhage with DIC

Intrapartum hemorrhage with DIC

Abortion

O45.0

O46.0

O67.0

O08.1

#ระชดของการแง เอใรสเฉพาะ

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Myelodysplastic Syndrome

Myeloproliferative Neoplasm

Bicytopenia

Pancytopenia

Bone Marrow Disorder

25

Bicytopenia

2 in 3 of Anemia or Neutropenia or Thrombocytopenia

ไรสเฉพาะ แพทไควรสปการจย

Coder องใ 2 รสวมน

D64.9 Anemia

D70 Agranulocytosis [PMN <1,000]

D69.6 Thrombocytopenia

“bi=Two, kyto=cell, penia=poverty”

Ambiguous Diagnosis

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Pancytopenia

Hemogloglin <13 gm% – male, <12 gm% – female

Total leucocyte count <4,000 cells/mL

Absolute neutrophil count <1,000 cells/mL

Platelet count <100,000mL

“pan=All, kyto=cell, penia=poverty”

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Pancytopenia“pan=All, kyto=cell, penia=poverty”

Mechanism Congenital Acquired


Gaucher’s disease

Fanconi’s anemia

Cytotoxic chemotherapy

Radiation therapy

Megaloblastic anemia

Bone marrow infiltration

Myelodysplastic syndrome

Myelofibrosis

Aplastic anemia

Increased DestructionLiver disease

Hypersplenism

Increased Destruction

&


Autoimmune disease

SLE, RA

Acute viral infections

CMV, EBV, HIV

HIV infections

Tuberculosis

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Pancytopenia

All of Anemia, Neutropenia and Thrombocytopenia

รสเหมาะสมไแ D61.9 Aplastic anemia, unspecified

หากตรวจพบสาเหแด ในกเนการจย

Hypersplenism

Drug-induced aplastic anemia – phenylbutazone, sulphonamide,

acyclovir, gancyclovir, chloramphenical, phenytoin, carbamazepine, nifedipine

Infections – HIV, Epstein-Barr virus, cytomegalovirus, parvovirus B19

Autoimmune disease – SLE, rheumatoid arthritis

Radiation, Chemotherapy

“pan=All, kyto=cell, penia=poverty”

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Pancytopenia


Pancytopenia due to

Aplastic anemia

Bone marrow infiltration

Congenital red cell aplasia

Drug-induced aplastic anemia

Radiation-induced aplastic anemia

Idiopathic aplastic anemia

Human immunodeficiency virus disease

Systemic infection

Autoimmune disease

Hypersplenism

!

D61.9

D61.8

D61.0

D61.1 + Y

D61.2 + Y84.2

D61.3

B23.2 + D61.8

D61.8

D61.8

D73.1

Pancytopenia in ICD-10-CM: D61.81

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Pancytopenia


Pancytopenia due to

Leukoerythroblastic anemia


Myeloproliferative disease

!

D61.8

D46.-

D47.1

Pancytopenia in ICD-10-CM: D61.81

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กมอาการเดความดปกเซลนำเดในไขกระก ง

งการเจญเบโต การฒนาการ และการำงานของเซล

ำใไขกระกไสามารถสางเดเอดแดง เดเอดขาว และ

เกดเอดไเยงพอ หอเยกา โรคไขกระกเอม

พบในคนอามากกา 60 เอบคงหงไแสดงอาการ

อาจเดจากการไบงและยาเคเยกา Secondary MDS

หอ Drug-induced MDS หอ Radiation-induced MDS

อาจเดจากการสารเคหอสารษ เน ยาาแมลง เบนน

เยกา Toxic-induced MDS

BM does not make enough mature blood cells

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Refractory anemia

Preleukemic anemia

Preleukemia

Refractory anemia with ringed sideroblasts

Refractory normoblastic anemia

Smoldering acute leukemia

Preleukemic syndrome

Subacute myelomonocytic leukemia

Chronic myelomonocytic leukemia

Hypoplastic acute myelogenous leukemia

Refractory anemia with excess myeloblasts

Hematopoietic dysplasia

Dysmyelopotic syndrome


1938 Rhoades and Barker

1949 Hamilton-Paterson

1953 Blaock et al

1956 Bjorkman

1959 Dacie el al

1969 Dameshek

1973 Saarni and Linman

1974 Sexauer et al

1974 Miescher and Farguet

1975 Beard et al

1976 Dreyfus

1978 Linman and Bagby

1980 Cohen et al

1980 Streuli et al

1982 Bennet et al

BM does not make enough mature blood cells

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Myelodysplastic SyndromeThe World Health Organization classification 2008

Disease Peripheral blood findings Bone marrow findings

Refractory cytopenia with

unlineage dysplasia (RCUD)

Refractory anemia (RA)

Refractory neutropenia (RN)

Refractory thrombocytopenia (RT)

Uni- or Bicytopenia

<1% blasts

Unileage dysplasia

<5% blasts

<15% ringed sideroblasts

Refractory anemia with ringed

sideroblasts (RARS)

Anemia

no blasts

Erythroid dysplasia

<5% blasts

>15% ringed sideroblasts

Refractory cytopenia with

multilineage dysplasia (RCMD)

Cytopenias (bicytopenia or

pancytopenia)

no or rare blasts

no Auer rods

<10x10

Dysplasia in >2 lineages

<5% blasts

<15% ringed sideroblasts

no Auer rods

34

Myelodysplastic SyndromeThe World Health Organization classification 2008

Disease Peripheral blood findings Bone marrow findings

Refractory anemia with excess

blasts-1 (RAEB-1)

Cytopenias

<5% blasts

no Auer rods

<10x10

Unilineage or multilineage

dysplasia

5-9% blasts

no Auer rods

Refractory anemia with excess

blasts-2 (RAEB-2)

Cytopenias

5-9% blasts

no Auer rods

<10x10

Unilineage or multilineage

dysplasia

10-19% blasts

+ Auer rods

MDS, unclassifiable Cytopenias

<1% blasts

no Auer rods

Unilineage dysplasia in

granulocytes or megakaryocytes

<5% blasts

no Auer rods

MDS associated with isolated

del(5q)

Anemia

<1% blasts

platelets normal or increased

normal to increased megakaryo-

cytic with hypolobated nuclei

<5% blasts

no Auer rods isolated del(5q)

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Myelodysplastic syndrome / MDS D46.9

Refractory anemia / RA

Refractory neutropenia / RN

Refractory thrombocytopenia / RT

Refractory anemia with ring sideroblasts / RARS

Refractory cytopenia with multi-lineage dysplasia / RCMD

Refractory anemia with excess blasts-1 / RAEB-1

Refractory anemia with excess blasts-2 / RAEB-2

MDS, unclassifiable

MDS associated with isolated del(5q)

D46.4

D46.7

D46.7

D46.1

D46.5

D46.2

D46.2

D46.7

D46.6

Refractory anemia with excess blasts in transformation C92.0

The World Health Organization classification

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Myeloproliferative DiseaseMyeloproliferative neoplasm (MPN), Myeloproliferative disorder (MPD)

กมความดปกเซลนำเดในไขกระกการเมำนวน

เซลเดเอดมากดปก

: Chronic myeloid leukemia (CML), Philadelphia chromosome positive

: Chronic neutrophilic leukemia

: Chronic eosinophilic leukemia / Hypereosinophilic syndrome

: Chronic idiopathic myelofibrosis

: Polycythemia vera

: Essential thrombocythemia

: Myeloproliferative disorder, unclassifiable

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Myeloproliferative DiseaseMyeloproliferative neoplasm (MPN), Myeloproliferative disorder (MPD)

38

Myeloproliferative Disease


Chronic myeloid leukemia, Philadelphia positive

Chronic neutrophilic leukemia

Chronic eosinophilic leukemia

Chronic idiopathic myelofibrosis

Polycythemia vera

Essential thrombocythemia

Myeloproliferative, unclassifiable

C92.1

D47.1

D47.5

D47.4

D45

D47.3

D47.1


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Myeloproliferative DiseaseThe World Health Organization classification

Chronic myelomonocytic leukemia (CMML) Ph-negative, BCR-ABL-negative disorder with monocyte count >1x10

Fewer than 20% blasts plus promonocytes in peripheral blood or bone marrow

Either dysplasia of one or more myeloid lineages or alternative criteria met (acquired

clonal cytogenetic abnormality or monocytosis persisting for at least 3 months and

alternative causes of monocytosis excludes)

Atypical chronic myeloid leukemia (aCML) Ph-negative, BCR-ABL-negative disorder with leucocytosis resulting from an increase in

neutrophils and their precursors, the precursors (promyelocyte to metamyelocytes)

consisting a least 10% of peripheral white cells

Basophils less than 2% of white cells

Monocytes less than 10% of white cells

Hypercellular bone marrow with granulocytic hyperplasia and dysplasia, with or without

dyplasia of other lineages


40


Juvenile myelomonocytic leukemia (JMML) Ph-negative, BCR-ABL-negative disorder with monocyte count >1x10


Plus two or more of the following

Hemoglobin F increased for age

Immature granulocytes in the peripheral blood

WBC greater than 10x10

Clonal chromosomal abnormality (monosomy 7 not excluded)

GM-CSF hypersensitivity of myeloid precursors in vitro

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Myelodysplastic/Myeloproliferative disease, unclassifiable One of the myelodysplastic syndromes are meet

There are prominent proliferative features (e.g. platelet greater than 600x10

>13x10

The condition has developed de novo

The criteria for other MDS/MPD (CMML, aCML, and JMML) are not meet

There is no Philadelphia chromosome, BCR-ABL fusion gene, 5q-, inv(3)(q21q26) or

t(3:3)(q21;q26)

42

Myeloproliferative Disease


Chronic myelomonocytic leukemia / CMML

Atypical chronic myeloid leukemia / aCMML

Juvenile myelomonocytic leukemia / JCMML

C93.1

C92.2

C93.3


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Leukemia

White Blood Cells

44

Acute Myeloid LeukemiaThe French-American-British (FAB) classification

Category Criteria

M0<3% of blasts MPO or SBB positive

Lymphoid markers negative

Immunological or ultrastructural features of myeloid differentiation

M1

Blasts >90% of bone marrow NEC

>3% of blasts MPO or SBB positive

Maturing monocytic component in bone marrow <10%

Maturing granulocytic component in bone marrow <10%

M2

Blasts 30-89% of bone marrow NEC

Maturing granulocytic component in bone marrow >10% NEC

Maturing monocytic component in bone marrow <20% of NEC or other

criteria of M4 not met

M3 Characteristic morphology

MPO: myeloperoxidase; SBB: Sudan black B; NEC: non-erythroid cells;

45


Category Criteria

M4

Blasts >30 of bone marrow NEC

Granulocytic component >20% of bone marrow NEC

Monocytic component >20% of bone marrow NEC and either PB monocytes

>5 x 10

proof of monocytic component

M5aBlasts >30% of bone marrow NEC

Bone marrow monocytic component >80% of bone marrow NEC

Monoblasts >80% of bone marrow monocytic component

M5bBlasts >30% of bone marrow NEC

Bone marrow monocytic component >80% of bone marrow NEC

Monoblasts <80% of bone marrow monocytic component


PB: peripheral blood smear

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Category Criteria

M6Erythroid cells >50% of BM cells

Bone marrow blasts >30% of NEC

M7 Blasts shown to be predominantly megakaryoblasts


PB: peripheral blood smear

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Acute Myeloid Leukemia


Acute myeloblastic leukaemia / AML

AML M0

AML M1

AML M2

AML M3

AML M4

AML M5

AML M5a

AML M5b

AML M6

AML M7

C92.0

C92.0

C92.0

C92.0

C92.4

C92.5

C93.0

C93.0

C93.0

C94.0

C94.2

The French-American-British (FAB) classification

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Acute Myeloid LeukemiaThe World Health Organization classification

Therapy-related AML and myeodysplastic syndrome* Alkylating agent related

Topo-isomerase II inhibitor related

Other types

AML with recurrent genetic abnormalities* AML with t(8;21)(q22;q22)/AML1-ETO fusion

AML with abnormal bone marrow eosinophils and inv(16)(p13q22) or t(16;16)(p13;q22)/

CBFB-MYH11 fusion

Acute promyelocytic leukaemia with t(15;17)(q22;q12)/PML-RARA fusion, and variants

AML with 11q23 rearrangement and MLL abnormality

AML with multilineage dysplasia* Following a myelodysplastic syndrome or a myelodysplasia/myeloproliferative syndrome

Without antecedent myelodysplastic syndrome

*If therapy-related cases have recurrent cytogenetic abnormalities, this is noted

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Acute Myeloid LeukemiaThe World Health Organization classification

AML, not otherwise categories AML, minimally differentiated (resemble FAB M0)

AML without maturation (resemble FAB M1)

AML with maturation (resemble FAB M2)

Acute myelomonocytic and acute monocytic leukaemia (resemble FAB M5a, M5b)

Acute erythroid leukaemia

Erythroleukemia (resemble FAB M6)

Pure erythroid leukaemia

Acute megakaryoblastic leukaemia (resembles FAB M7)

Acute basophilic leukaemia

Acute panmyelosis with myelofibrosis

Myeloid sarcoma (granulocytic or monocytic)

#Defined as having at least 50% of cells dysplasia in at least 2 lineages

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AML with t(8;21)

AML 1/ETO

AML with eosinophils with inv(16) or t(16;16)

Acute promyeloblastic leukaemia with t(15;17) and variants

AML with 11q23 rearrangement and MLL abnormality

AML with multilineage dysplasia

C92.0

C92.0

C92.5

C92.4

C92.6

C92.8


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AML, minimal differentiation

AML without maturation

AML with maturation

Acute monoblastic leukaemia

Acute monocytic leukaemia

Erythroleukaemia

Pure erythroid leukaemia

Acute megakaryocytic leukaemia

Acute basophilic leukaemia

Acute panmyelosis with myelofibrosis

Myeloid sarcoma

C92.0

C92.0

C92.0

C93.0

C93.0

C94.0

C94.0

C94.2

C94.7

C94.4

C92.3


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Bleeding Disorders - banponghospital · Bleeding Disorders Clinical Features Platelet Disorders...

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