7.Hematology Summary

8/2/2019 7.Hematology Summary

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Hematology summary


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Index

1. Anemia

2. Lymphoma

3. TTP4. DIC

5. Myeloproliferative disorders


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Anemia


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Index = Reticulocyte index


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IDA

A 29-year-old female has become increasingly lethargic for the past 6 months.

She complains from SOB, fatigue and tachycardia.

She reported a heavy menstrual cycle and denied any previous history of

melena or hematemesis .

On physical examination she was afebrile.


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1. Identify the condition? Iron deficiency anemia

2. Causes:

Blood loss from the menstrual cycle . Other causes of IDA include:

Poor intake

Increased demand (growth and pregnancy)

Decreased absorption (small bowel disease or after gastrectomy)

3. DDx? other causes of Hypochromic Microcytic anemia: Anemia of chronic disease (could be normochromic normocytic also)

Thalassaemia.

Sideroplastic anemia. (Prussian blue iron stain of the bone marrowshows ringed sideroblasts, which are nucleated red blood cellprecursors with perinuclear rings of iron-laden mitochondria. Look to

this figure)


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4. Clinical Presention:

In acute blood loss (hypovolemia)

Hypotension

Decreased organ perfusion

Chronic onset vary with the

Age

Adequacy of blood supply to critical

organs.

Moderate anemia is associated with

Fatigue, loss of stamina Breathlessness

Tachycardia

Pale skin & mucous membranes

Decreased epithelial iron

Brittle hair & nail

Atrophic glossitis

Angular stomatitis

Rarely seen

Paterson-Brown-Kelly syndrome

(Pharyngeal webs causing dysphagia)

Koilonychia (Spoon-shaped nail)


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5. Investigation: Blood count: low Hb & low MCV

Blood film ; microcytic, hypochromic, with anisocytosis &poikilocytosis.

Serum ferritin (reflect iron stores) is low

Serum iron is low

Total iron binding capacity (TIBC) is high resulting in atransferrin saturation < 19%

Serum soluble transferring receptor: increase in IDA. Bone marrow examination is only necessary in complicated

cases and shows erythroid hyperplasia and absence ofiron.

Micocytic

Hypochromic

Anisocytosis and poikilocytosis


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6. Management

Find and treat the underlying cause.

Oral iron

Parenteral iron

Rarely necessary

Pts are intolerant Poor response to oral iron (severe malabsorption)

Thalassaemia and Sideroblastic anemia:

Accumulation of iron

Increases serum iron and ferritin

Low TIBC


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Megaloblastic Anemia

A 26 years old male presentedto your clinic complaining fromAnorexia , weight loss anddiarrhea. Taking historyrevealed that he is vegan and

alcoholic.

Physical examination showsglossitis , angular stomatitis ,slight skin brusining andparasthesia in the tip of his

fingers. Past medical hx reveals

recurrent URTI during the last 6months.


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1. Identify the condition: Megaloblastic anemia due to B12 deficiency

2. Causes: Low dietary intake: Vegans

Impaired absorption: Stomach : Pernicious anemia / Gastrectomy

Small bowel : Ileal disorder or resection / celiac disease / tropicalsprue /Bacterial overgrowth.

Congenitaltranscoblamine II deficiency (rare).

3. DDx: Megaloblastic : B12 deficiency or Folate Deficiency.

Normoblastic : Myelodysplasia , hemolysis (inc, retics).

Other defect ofDNA synthesis , e.g. chemotherapy.


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4. Clinical presentation

Symptoms ofanemia (previously mentioned).

Mildjaundice.

Anorexia , Weight loss , diarrhea or constipation

Glossitis (red sore tongue).

Polyneuropathy caused by symmetrical damage to the

periephral nerve.

Subacute combined degeneration of the spinal cord.pts arepresented with progressive weakness , ataxia and paraplegia.

Optic atrophy may cause dementia and visual disturbances.

Thrombocytopenia & leucopoenia.

Glossitis:

Folic acid

deficiency

Glossitis:

Pernicious

anemia.


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5. Investigation: Blood count: severe cases leucopoenia and thrombocytopenia.

Blood film : Macrocytic anemia with hypersegmentedneutrophil nuclei

serum B12: Low

Red cell folate may be reduced.

Serum billirubin may be increased.

BM examination shows a hypercellular BM with megaloblasticchanges.

HypercellularBM with megaloblastic changes

Hypersegmented neutrophils


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6. Management:

B12 deficiency: IM vitamin B12.

Oral B12 (dietary deficiency)

Folic acid deficiency: Oral folic acid (higher doses in malabsorption).

Undetermined megaloblastic anemia:

folic acid alone may aggravate the

neuropathy of B12 deficiency, so give both


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Thalassemia

Prominent MaxillaTarget cells

Bull's-eye appearance

X ray shows:Hair like in the periphery of skull,

which indicate BM hypertrophy.


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1. Identify the condition:

Thalassemia.

2. Cause:

Inherited disorders Impaired synthesis of one or more of the polypeptide chains of

globin.

3. DDx:

Other causes for microcytic hypochromic RBC's.

4. Clinical picture:

Vary from hematologic abnormality severe and fatal anemia.

In B thalassemia major

Severe anemia presents in the 1st year of life

FTT Recurrent infection.

Prominent maxilla, frontal & parietal bones (Hypertrophy BM).

Hepatosplenomegaly.


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5. Investigation: (Homozygous disease)

Blood count: raised reticulocyte count

Blood film: hypochromic, microcytic anemia , nucleatedred cells in the periephral circulation.

6. Diagnosis:

Hb electrophoresis, which shows

Increase in Hb F.

Absent or markedly reduced Hb A.

7. Management:

Homozygous pt : blood transfusion.

Some cases :BM transplantation.


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Normal


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IDA

Low Hb Low MCV (microcytic)

Low MCH (hypochromic)

High RDW

(poikilocytosis)


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Megaloblastic Anemia

Markedly increased MCV

Mildly increased

Blood loss

Hemolytic anemia


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MICROANGIOPATHIC HEMOLYTIC

ANEMIA(MAHA)

Low RBC

Low HCT

High RDW

Blood film:Schistocytes

(fragmented RBC)


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SPHEROCYTOSIS

Small & rounded RBC (not

biconcave), so increased Hb

content.

High MCHC DDx:

Autoimmune hemolytic

anemia


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Severe anemia who underwent

transfusion

Dual populations

of RBCs

Low RBC

High MCV (inc. retics)

High MCH

HIGH RDW


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Lymphoma

HD & NDL


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Epidemiology of lymphomas

5th most frequently diagnosed cancer overall for both malesand females

males > females

Mechanisms

Genetic alterations Infection

Antigen stimulation

Immunosuppression cyclosprine

incidence NHLincreasing over time

B-cell (70%)

T-cell (30%)

Hodgkin lymphoma stable


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Hodgkins disease

More common in Males

Caucasian

Late 20th & >45y.

Spread by contiguous Etiology:

Viral infection: EBV, HIV

Pathology

Reed-Sternberg cells Lymphocytes, histiocytes,

neutrophila & eosinphils.

WHO classification

1. Nodular lymphocytepredominant HL (5%)

Cervical & inguinal

involvement Frequent relapse

Good prognosis, rarelyfetal

2. Classical HD

Nodular sclerosis Lymphocytes Rich

Mixed cellularity

Lymphocytes depleted


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A possible model of pathogenesis

germinal

centre

B cell

transforming

event(s)

loss of apoptosis

RS cellinflammatory

response

EBV?

cytokines


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Classical HD

Nodular sclerosis HD:

Most common type

More in females

Associated with

Mediastinal mass Hilar lymphadenopathy

Neck

Good prognosis (stage I,II)

Histology

Fibrosis

Lacunar cells

Lymphocytes Rich

Uncommon

Good Prognosis (stage I, II)

Mixed cellularity: More in older people

2nd most frequent

Prognosis fair (stage III)

Lymphocytes depleted Rare

Poor prognosis (stage III,IV)


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RS cell and variants

popcorn celllacunar cellclassic RS cell

(mixed cellularity) (nodular sclerosis) (lymphocyte

predominance)


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Reed-Sternberg cell

Reed-Sternberg cells may be

found in:

NHL Benign illnesses

Carcinoma


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Clinical Lymphadenopathy, 4%

have limited diseasesbelow the diaphragm Non-tender (painless) Firm, rubbery

Rarely the patients maypresent with Auto immune

thrombocytopenia Auto immune hemolytic

anemia

Hepatosplenomegaly

Thromboembolic disease Viral > bacterial infection

B symptoms associatedwith poor prognosis andadvanced disease. Fever > 38C Drenching night sweats Weight loss (>10%)

Anorexia, fatigue Purities Alcohol induced pain

Contiguous involvement Cough

SOB

LN biopsy is the definitive diagnosis RS cells

CT scan for staging

Gallium scan to asses the response oftreatment


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Investigations

1. Laboratory tests CBC

Anemia

Lymphocytopenia (replacementof LN structure)

Neutrophilia, eosinophilia

Thrombocytosis orthrombocytopenia.

LFT may be abnormal

Chlestatic pattern, non caseatinggranuloma

Live involvement with HD

LDH may be elevated due to

Disease activity

Organ involvement

ESR, Serum ferritin, and B2 microglobulin are elevated in patients with

advanced disease.

2. CXR

Mediastinal widening

3. CT scan

Intrathoracic nodes (70%)

For staging

4. BM aspirate

Advanced disease

Anemia, high ESR.

B symptoms, Stage IV

5. PET

Staging & disease activity


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DDx

Lymphadenopathy Lymphoma

TB

Brucellosis

Metastatic carcinoma Sarcoidosis

Hx: Site, size & shape

Colour

Temp. & tenderness Consistency

Mobility

Relations

Eosinophilia Lymphoma

Vasculitis

Parasitic infection

Allergic reaction Elevated LDH:

Lymphoma

Acute leukemia

Hemolytic anemia


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Staging:

1. History

2. PE

LN

Spleen

Liver

3. Blood studies

4. Imaging studies

Mediastinal

lymphoma

3 Stage III


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1. Stage I

Single LN region

Singleextra lymphatic organ

2. Stage II

2 or more LN regions on thesame side of the diaphragm

Localized involvement of the

extra lymphatic organ.

3. Stage III

LN regions on both side of thediaphragm.

Localized involvement ofextralymphatic organ

Spleen involvement

4. Stage IV

Diffuse involvement of 1 ormore extra lymphatic organs

LN enlargement

Liver or BM involvementis always consideredstage IV

A. Absence of B symptoms

B. Presence of B symptomsE. Extra nodal site by localextension

X. Bulky disease: mediastinal widening

>1/3 at T6-7 >10 cm in any

single dimension.

Stage I Stage II Stage III Stage IV

Staging


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Treatment1. Radiotherapy

Early stage

I, II without B symptoms

2. Chemotherapy Stage B

3. Combined modality treatment

Early staged some poor

prognostic factors.

Massive mediastinal involvement.

4. BM transplantation

Chemotherapy side effects:

Cyclophosphamide: hemorrhagic

cystitis Anthracyclines: cardiomyopathies

Bleomyocin: pulmonary fibrosis

Vinca alkaloids: neuropathies

BM suppression (long period)

Infertility

Radiation side effects: Mouth

Stomatitis

Oral thrush

Thyroid

Hypothyroidism

Lung

Radiation pneumonitis

Pulmonary fibrosis

Cardiac disease

Pelvic irradiation

Infertility

2ndmalignancies

Sarcomas, lung, skin cancer


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NHLRisk factors

immunosuppression orimmunodeficiency

Ionizing radiation

Infectious agents

CT disease

Family Hx of lymphoma

Complication:

CNS infiltration

BM failure

Immune hemolysis orthrombocytopenia

Bulky disease, compression of

structures as spinal cord, ureters

pleural/pericardial effusions

Ascites

Clinical manifestations

Asymptomatic

Systemic B symptoms:

Fever

Night sweats

Weight loss

Anorexia

Pruritis

Local manifestations

Lymphadenopathy

Splenomegaly most common

any tissue potentially can be

infiltrated

Cli i l f t


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Clinical features

Adenopathry

Extra nodal

CNS

Thyroid

Mediastinal

Lung

Abdominal masses

Testes BM especially with indolent

low grade lymphomas.

Skin (esp. T cells:

Mycosis fungoides

Sezary syndrome

Renal failure (tumor lysis

syndrome)

Lab investigations

CBC leukaemic phase of

lymphoma

LDH

ESR, B2 micro globulin

IG

LFT

KFT

Diagnosis

Tissue biopsy

Flowcytometry

Cytogenetics

Radiological CT

MRI

Gallium scan

Staging is not useful.


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Lymphoma classification(based on 2001 WHO)

1. B-cell neoplasms (70%) Precursor B-cell neoplasms (2 types)

Mature B-cell neoplasms (19)

B-cell proliferations of uncertain malignant potential (2)

2. T-cell (30%) & NK-cell neoplasms Precursor T-cell neoplasms (3)

Mature T-cell and NK-cell neoplasms (14)

T-cellproliferation of uncertain malignant potential (1)

3. Hodgkin lymphoma Classical Hodgkin lymphomas (4)

Nodular lymphocyte predominant Hodgkin lymphoma (1)

Neoplasms of lymphoid origin, typically causinglymphadenopathy

Clonal expansions of cells at certain developmental stages


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A practical way to think of lymphoma

Category Survival of

untreatedpatients

Curability To treat or

not to treat

Non-Hodgkin

lymphoma

Indolent Years Generally

not curable

Generally

defer Rx if

asymptomatic

Aggressive Months Curable in

some

Treat

Very

aggressive

Weeks Curable in

some

Treat

Hodgkin

lymphoma

All types Months to

years

Curable in

most

Treat


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B-cell development

stem

cell

lymphoid

precursor

progenitor-B

pre-B

immature

B-cell

mature

naive

B-cell

germinal

center

B-cell

memory

B-cell

plasma cell

DLBCL,FL, BL, HL

LBL, ALL

CLLMCL

MM

MZL

CLL


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Follicular lymphoma

Most common type of indolent lymphoma 20% of B cell lymphoma Often asymptomatic Associated with BCL-2 gene rearrangement [t(14;18)]

Cell of origin: germinal center B-cell Not curable (some exceptions) Treatment

Asymptomatic(watch-and-wait) Symptomatic: chemotherapy

Death due to Transformation to aggressive lymphoma Therapy


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Diffuse large B-cell lymphoma

Most common type of aggressive lymphoma

Usually symptomatic

Extranodal involvement is common

Cell of origin: germinal center B-cell

Treatment should be offered

curable in ~ 40%


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Chronic lymphoid leukaemias

Most common type of leukaemia in

elderly

M:F 2:1

Majority asymtomatic

Etiology:

1. Genetic factors : familial cases,

west

2. Immunological factors :

Inherited and acquired

immunodeficiency are often

associated with CLL, and otherLPD

Clonal disease of mature

lymphocytes

Peripheral blood shows:

Persistent lymphocytosis

Small mature lymphocytes

B symptoms are rare Pulmonary leukaemic infiltrate are

common

BM infiltration

CD5 positive ,weak expression of SIg

Richter syndrome (5%) Transformation to large cell

lymphoma

Clinical features:

Fever

Weight loss Increased localized or

generalized

lymphadenopathy.


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Trisomy

BM


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Clinical Manifestations

25% symptomatic

A Symmetrical enlargement of LN

Mobile

Non tender

Mainly involving the supraclavicular, axillary & inguinal region. Obstructive manifestations

Splenomegaly (50%).

Immunodeficiency (recurrent infections as Herpes Zoster)

Hypogammaglobulinaemia

Bacterial infections (e.g. S.pneumonia, S.aureus, H.infleunzae,Pneumocystis Carinii)

Hypervicosity due to increase lymphocytes count.


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Immunologic abnormalities : Decreased gamma globulins

Impaired granulocytesfunction

Impaired T cell function Coombs positive hemolytic

anemia (10%)

Immune thrombocytopenia(5%)

Rarely immune neutropenia& pure red cell aplasia

Increased incidence ofsecondary malignancy e.g.skin cancer

Poor prognostic factors : Lymp. count> 50x 10/l Lymp. doubling time < 12

months Prolymphocytes >10%

BM histology diffuse type Cytogenetics Trisomy 12 Age > 70 years Sex male High level ofB2 micro

globulins Anaemia &

thrombocytopenia due toBM infiltration


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Management

Usually indolent1. Persistent or progressive symptoms ( fever, night

sweats, weight loss)

2. lymphadenopathy causing mechanical obstruction

or cosmetic deformities3. Progressive enlargement of LNs, spleen & liver.

4. Stge III,IV

5. Immune hemolytic anemia or thrombocytopenia

6. Rapid lymphocytes doubling time.


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Multiple myeloma

Less common than NHL

>15% of BM is plasma cells

Plasma cell function:

Igs production

Osteoclast activation Lytic bone lesion

Hyper-Ca

RF

Clinical features:

BM faliure

Elevated Igs

Hypercalcemia

RF

Bone disesase Lytic lesions

Dec. bone density

Hyperviscosity syndrome

Recurrent infections

Amyloidosis

Heavy proteinuria (NS)

Malabsorption

Large tongue

Splenomegaly

Bleeding tendency

Diagnosis:


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Diagnosis:

BM biopsy (inc. plasma cells)

Serum protein electrophoresis (monclonal bands)

Skeletal survey (lytic lesions & hyper-Ca)

Quantitative Igs

Hyperviscosity syndrome:

Due to increase in

Cells (polycythemia & leukemia)

Proteins

Multiple myeloma (IgA & IgG3)

Waldenstrom macroglobulinemia (IgM)

Lymphadenopathy Splenomegaly


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THROMBOCYTOPENIA


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Hematoma

Petechiae

Investigations: plt. count

PurpuraEcchymosis

If normal PT & PTT Trombocytopenia
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Thrombocytopenia Plt < 150 x 109/L

May be caused by:

1. Decreased platelet production

BM infiltration (malignancy,

myelofibrosis, gauchers disease)

Aplastic anemia/Paroxysmal

nocturnal hemoglobinuria

Viral infection (HIV, CMV,

hepatitis)

Chemo-/Radiotherapy

Alcohol (direct toxicity, folate

deficiency)

Folate & Vitamin B12 deficiency

Myelodysplastic syndrome

Congenital thrombocytopenias

(Fanconis anemia, TAR, Wiskott-

Aldrich syndrome)

2. Increased platelet destruction Immune:

ITP

Drug-induced (quinidine, heparin-HIT)

Malaria-associated

Non-immune: TMA

DIC

Inflammatory platelet activation

(malignancy, sepsis)

3. Platelet sequestration Normally 30% of platelets reside in the

spleen

Splenomegaly of any etiology ( infection,

storage disease, malignancy, congestion)

may produce pancytopenia, a syndrome

termed Hypersplenism.
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Hypersplenism (signs)

1. Splenomegaly

2. Pancytopenia

3. Normal/hyperplastic BM4. Respond to splenctomy

Causes:

Hemolytic anemia

Portal HTN

Leukemia Lymphoma

Splenomegaly

Infections

Inflammation (SLE, RA &

sarcoidosis) Haemtological

Portal HTN

Miscellaneous Storage disease

Neoplasia Amyloidosis

Low plt. & splenomegaly, not: ITP

Aplastic anemia


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ITP

Incidence 1:10,000 Peak incidence:

3-5y ( M/F 1:1)

20-30y ( M/F 1:3)

Chronic, insidious disease

Caused by auto-antibodies,which bind to platelets IIb/IIIaglycoprotein receptor

Antibody-coated plt. clearedfrom circulation by spleen.

Primary ITP

Secondary:

SLE

Lymphoproliferativedisorders (esp. CLL &Hodgkins disease)

GVHD

Myasthenia Gravis

Viral infection (HIV..)


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ITP in Adults

Sx:

Easy bruising of several mon.

Petechiae/purpura (esp. over

dependent parts)

Mucosal bleeding

Epistaxis

Hematuria

Melena

Heavy menses

Internal bleeding (rare)

No

Splenomegaly

Lymphadenopathy

Laboratory results

Thrombocytopenia

Normal WBC

Normal coagulation studies

Peripheral smear

Large platelets

BM examination:

Inc. megakaryocyte count

NormalErythroid &

myeloid development.
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Diagnosisof Primary ITP is by exclusion.

Isolated thrombocytopenia DDx:

Secondary ITP Hypersplenism

Drug-induced thrombocytopenia

TMA

Pseudothrombocytopenia
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Treatment

1. Steroids prednisone:

Impaired clearance of antibody-

coated platelets by RES

Inhibition of antibody

production

Increased platelet production

Stabilization of vessel wall

2. IVIg & Anti-D Ig

Not achieve cure

Emergencies

Preparation for splenectomy

Management of patients

resistant to other therapeutic.

3. Splenectomy Steroid-dependent Steroid-resistant

Failing splenectomy:4. Look for accessory spleen5. Immunosuppression

Vincristine

Azathioprine Cyclophosphamide

6. Danazole (weak androgen)7. Cyclosporin A8. Rithuximab (Mabthera)Emergency treatment9. Platelet transfusion

10. IV steroids11. IVIg12. Anti-fibrinolytic agents13. Emergency splenectomy


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ITP in Pregnancy

Incidence: 1-2/1000 deliveries

Chronic ITP often exacerbates

during pregnancy

Plt

> 30,000 suffice for delivery

> 50,000 are required CS

Antibodies ( IgG ) cross the

placenta and may cause

severe thrombocytopenia inthe fetus

DDx of thrombocytopenia inpregnancy:

Gestational (4% 3rd trimester)usually Plt>75,000)

ITP

Preeclampsia (incl. HELLPsyndrome)

Von Willebrand disease (type IIb)

Treatment of ITP in pregnancy:

Steroids

IVIg

Splenectomy (should be avoidedunless necessary)

Immunosuppressive drugs arecontraindicated

Th b ti Mi i thi


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Thrombotic Microangiopathies

(TMA)

Incidence: 3,5:10,000

F/M 3:2

Peak incidence: 3rd decade

Mortality

100% without treatment

15% with treatment

1. Primary (abs against ADAMTS13) Thrombotic Thrombocytopenic

Purpura-TTP

2. Secondary (enzyme is depressed)

Verotoxin associated (HemolyticUremic Syndrome-HUS)

Malignancy and chemotherapyassociated

HIV associated

BM transplantation (BMT) associated

Drug associated

Pregnancy associated

Autoimmune associated

Neuraminidase-associated

3. Hereditary (enzyme deficiency)

Upshaw schulman syndrome

Thrombotic Thrombocytopenic


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Thrombotic Thrombocytopenic

Purpura

Classical Pentade of Findings:

1. Microangiopathic hemolytic anemia (sin qua non of the

disease)

2. Thrombocytopenia - may be quite severe (


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Initiating factors are unknown

Endothelial wall damage

Inducing platelet aggregation

Production ofultra-large

multimers ofvWF supporting

platelet aggregation (most

imp.)

UL-vWF multimers are

normally cleaved by a vWF-

cleaving protease, encoded on

chromosome 9

Familial TTP, congenital

deficiency of the enzyme

Acquired TTP, its activity is

inhibited by neutralizing

antibodies (autoimmunity)

Other factors involved: Increased endothelial

production & release ofplatelet-activating proteins(calpain)

Impaired endothelialproduction & increaseddegradation ofprostacyclin

Anti-endothelial cellantibodies

Apoptosis of endothelial cells

with predilection to renal &cerebral vasculature)

Factor V Leiden (micro-thrombosis)


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Treatment:

Plasmapheresis

90% response within 3 weeks

30% relapse months to years after initial episode

Splenectomy (for refractory disease)

Steroids (effective only in conjunction with apheresis)

Anti-platelet agents (aspirin, clopidogrel)

Platelet transfusions are CONTRAINDICATED bcz abs


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Hemolytic-Uremic Syndrome

Induced by infection withverotoxin-producing

E.Coli (esp. 0157:H7)

Shigella

Causing

Endothelialdamage

Secondary platelet activation

Formation ofthrombi in renalmicrovasculature

Incidence: highest


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TMA - malignancy and chemotherapy

associated

Disseminated malignantneoplasms

Esp. adenocarcinomas of

GIT

No effective treatment

exists

The survival is measured in

weeks (unless responds to

treatment)

TMA caused by

chemotherapeutic

agents

Especially Mitomycin C Responds to

plasmapheresis in 20-

50%;

Mortality is >50% in 2

months


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TMA

HIV associated 20% of AIDS patients

develop TTP

Pathogenesis Endothelial

damage by Opportunistic infections

Drugs

HIV itself

Plasmapheresis is beneficial

Prognosis is generally poor(about 1 year)

TMA

BMT associated Develops in 5% of bone

marrow recipients

May be caused by

Irradiation Cyclosporin A

GVHD

Prognosis depends on theseverity of the disease

Plasmapheresis is indicated,but its benefit is unclear


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TMA - other

Drug-associated (quinine, ticlopidine, clopidogrel)

Pregnancy-associated (10% of TTP; chronic diseasecan be exacerbated by pregnancy)

Autoimmune disease-associated

Neuraminidase-associated (enzyme secreted byStreptococci)

DISSEMINATED INTRAVASCULAR


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DISSEMINATED INTRAVASCULAR

COAGULATION

Clinical picture Bleeding from any where, spontonous.

5-10 % microthrombotic lesions Gangrene of fingers, toes, renal arteriols.

PATHOGENESIS:

DIC occurs when the compensatory mechanisms of haemostasis havebeen overcome.

The triggering mechanisms:

1. Entry of tissue thromboplastin into the blood stream, following extensivetissue trauma, malignant disease, massive blood transfusion.

2. Direct activation offactor X or prothrombin (Factor II) by snake venoms.

3. Severe vascular endothelial injury in patient with gram negativesepticaemia.

4. Directplatelets activation


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depletion of clotting factors

prolonged PT, PTT

increased FDP and D-dimer

thromboctyopenia (consumption)

LABORATORY

MANIFESTATIONS

microangiopathic hemolytic anemia

decreased fibrinogen

depletion of physiologic anticoagulants

tissue factor release

activation of extrinsic

pathway of coagulation

(systemic thrombin

generation)

generalized intravascular

fibrin deposition

underlying disorder

activation of

fibrinolytic system

(systemic plasmin generation)

PATHOPHYSIOLOGIC

EVENTS

Pathophysiology of DIC

hemorrhage

thrombosis/infarction

CLINICAL

MANIFESTATIONS


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CauseAcute

Shock

Sepsis

Allergic reactions

Mismatched transfusion

Obstetrical problems Trauma

Burns

Extracorporeal circulation

Acidosis

Purpura fulminans

Decreases in both coagulants &

anticoagulants

Severity may relate to levels of

anticoagulants

Subacute/Chronic Acute leukemia

Carcinomas

Hemangiomata

Aortic aneurysms

???? liver disease


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Diagnosis

Thrompocytopenia Prolongation ofPT & aPTT

Low Fibrinogen

Fibrin split products D-dimer RBC fragmentation

Other tests

Low level ofAnti thrombin III

Low level ofprotein C Thrombin/ Anti thrombin III complex


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Treatment

Depends on primary manifestation Thrombosis - Anticoagulant therapy

Heparin

Bleeding - Replacement therapy

Cryoprecipitate - Fibrinogen Fresh frozen plasma - Other factors

Platelets

Primary treatment

TREAT UNDERLYING DISEASE

Thrombocytopenia


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y p

Pseudo? True?(Perform smear)

WBC, HbPT/PTT

Physicalexamination

Normal

Leukemia?

High WBC LowWBC/Hb

MCV-N MCV

Vitamin B12deficiency?

MDS?

PTT

DIC?

Splenomegaly

Hypersplenism?(look for cause)

ITP?(consider

bone marrowaspiration)

No need towork up

Fragmented RBCs

TMA?


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Myeloproliferative disorders

Chronic


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Chronic

Clonal disorders of hemopoietic stem cells

Over-production of all cell lines, with usually one line in

particular Fibrosis is a secondary event

Acute Myeloid Leukemia may occur

Splenomegaly is the major physical sign

Include

1. Chronic myeloid leukemia

2. Polycythemia (Rubra) Vera (PRV, PV)

3. (Primary) Essential Thrombocythemia

4. Myelofibrosis (with Myeloid Metaplasia), AgnogenicMyeloid Metaplasia (MF,MMM, AMM)


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Chronic Myeloid leukaemia CML

Proliferation of all haematopoietic lineages, predominantly inthe granulocytic cell line, without the loss of their capacity to

differentiate.

Occurs 30 to 80 y.

More common in males

The aetiology is unknown.

Blood film:

All stages of maturations Majority are myelocytes &

neutrophils

In CLL, majority are lymphocytes


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Clinical features

Asymptomatic (25%)

Anorexia, Wt loss, lassitude,

night sweats

Splenomegaly

Anaemia, pallor, dyspnoea,

tachycardia

Bruising, epistaxis,

menorrhagia

Gout, renal impairment

Cytogenetic and molecular aspects:

1. Philadelphia chr.

2. Reciprocal translocation

between chromosome 9 & 22 in

region calledBCR carried ABL

oncogene.

Management

1. Curative treatment:

Allogeneic BM transplant, but

it is still not completely curable.2. Control treatment:

Imatinib, inhibit BCR-ABL

activity but it is very expensive

3000 JD\month

Hydroxyurea & interferon.


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Natural Hx1. A chronic phase (85%)

Duration 3-4 years

Splenomegaly

Leukocytosis

Easily controlled

The major goal of treatmentis to control symptoms and

complications resulting from

Anemia

Thrombocytopenia

Leukocytosis

Splenomegaly

Newer forms of therapy aim

at delaying the onset of the

accelerated or blastic phase,

2. Accelerated phase

Emergence of a discrete blast

cell population

blast < 20%

Left shift

3. Blast phase

>30% blasts

Promyelocytes in peripheral

blood or marrow.

Normal marrow erythropoiesis Megakaryopoiesis reduced.

Disease transformed into

AML (70%)

ALL (30%)


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Chronic phaseAccelerated phase

Blast phase


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Case presentation

A 49yr old teacher, saw her physician because of

fatigue for about six months.

Physical exam Showed little except for pallor,

normal temperature, and massive splenomegaly.Blood tests were ordered to investigate possible

anaemia. Laboratory results indicated a high

white count consistent with Chronic MyeloidLeukaemia.

E ti l Th b th i


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Essential Thrombocythemia Constitutive production ofthrombopoietin by liverraised level of

dysfunctional circulating platelets

Plt. > 600 at least 2 months

Diagnosis by exclude reactive causes

Clinical

Thrombosis Erythromelagia

painful big toe

CVA

TIA

Stroke

Bleeding

Management

Aspirin (thrombosis)

Hydroxyurea

WBC x 109/L 10.0 [4-11]


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[ ]

Hb g/L 156 [140-180]

MCV fl 85 [80-100]

Platelets x 109

/L 1560 [150-450] Neuts x 109/L 7.0 [2-7.5]

Lymphs x 109/L 2.0 [1.5-4]

Monos x 109/L 0.8 [0.2-0.8]

Eos x 109/L 0.1 [0-0.7]

Basos x 109/L 0.1 [0-0.1]

Blood film: many large and abnormalplatelets

P l h i R b V (PRV)


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Polycythemia Rubra Vera (PRV)

Excessive production of all myeloid cell lines,predominantly red cells.

PRV masked by IDA.

Clinical features

Increase in whole blood viscosity causes Vascular occlusion

Ischemia

Headaches, Itch

Thrombosis, TIA, stroke

Splenomegaly

Di iSecondary PRV

d


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Diagnosis

1. Raised red cell mass (PCV)

Males PCV>51%

Females PCV >48%

2. Normal plasma volume

level

3. Normal or low

erythropoietin

4. O2% >92%

5. Splenomegaly & central

cyanosis

Hypoxia due to

Chronic lung diseases,

Congenital heart disease

VSD

Renal cell carcinoma which

leads to increase

erythropoietin synthesis,

Diuretics therapy (reduction inplasma volume)

Smokers

WBC x 109/L 18.0 [4-11]


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[ ]

Hb g/L 200 [140-180]

HCt 0.62 [.42-.51]

MCV fl 75 [80-100]Platelets x 109/L 850 [150-450]

Neuts x 109/L 14.6 [2-7.5]

Lymphs x 109/L 2.0 [1.5-4]

Monos x 109/L 0.8 [0.2-0.8]

Eos x 109/L 0.1 [0-0.7]

Basos x 109/L 0.5 [0-0.1]

Management

1. Phlebotomyvenesection to decrease viscosity, repeated every 5-7 daystill hematocrit become less than 0.45

2. low-dose aspirin (controversial) - 80 mg/day

3. Hydroxyurea if necessary

4. Do not treat with iron

Blood film:

Microcytosis Large and abnormal

platelets

M l fib i (MF)


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Myelofibrosis (MF) Characterized by

BM fibrosis

Extramedullay haematopoiesis

Leukoerythroblastic blood picture

BM failure

WBC x 109/L 2.4 [4-11] Hb g/L 88 [140-180]

MCV fl 85 [80-100]

Platelets x 109/L 60 [150-450]

Neuts x 109

/L 1.0 [2-7.5] Lymphs x 109/L 1.0 [1.5-4]

Monos x 109/L 0.2 [0.2-0.8]

Eos x 109/L 0.1 [0-0.7]

Basos x 109/L 0.1 [0-0.1]

Clinical:

BM failure SplenomegalyDiagnosis

Typical blood picture Splenomegaly Dryaspirate Fibrosis on trephine

biopsy Absence of other causeTreatment:

Supportive care Splenectomy if

necessary

Blood film:


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A few nucleated red cells

Myelocytes (leukoerythroblastic)

Tear-drop (poikilocytes)

C 1


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Case 1

50 year female patient presented to ER,complaining ofpainful big toethis is a

CBC for her:

WBC x 109/L 10.0 [4-11]

Hb g/L 156 [140-180]

MCV fl 85 [80-100]Platelets x 109/L 1560 [150-450]

Neuts x 109/L 7.0 [2-7.5]

Lymphs x 109/L 2.0 [1.5-4]

Monos x 109/L 0.8 [0.2-0.8]

Eos x 109/L 0.1 [0-0.7]Basos x 109/L 0.1 [0-0.1]

DDx: Essential thrombocytothemia

Secondary: Chronic Myeloid Leukaemia

Post splenectomy

Malignancy

Inflammatory diseases (eg.rhumatoid)

Bleeding

Anaemia

Clinical

Erythromelagia

Peripheral Vascular occlusion

Transient Ischemic Attack (TIA)

Stroke Bleeding (esp. surgical)

PE

Splenomegaly

C 263 smoker male patient presented to a

clinic complaining ofheadache, &


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Case2p g ,

this is a CBC for him:

WBC x 109/L 18.0 [4-11]

Hb g/L 200 [140-180]

HCt 0.62 [.42-.51]

MCV fl 75 [80-100]

Platelets x 109/L 850 [150-450]

Neuts x 109/L 14.6 [2-7.5]

Lymphs x 109/L 2.0 [1.5-4]

Monos x 109/L 0.8 [0.2-0.8]

Eos x 109/L 0.1 [0-0.7]

Basos x 109/L 0.5 [0-0.1]

DDx:

Primary: Polycythemia (Rubra) Vera Secondary:

Smoking, COPD

Diuretics

Cyanotic heart disease, PCKD

Renal cell carcinoma

PE & investigation:

PCV

Plasma volume

Erythropoietin level

Oxygen saturation

US for spleen, liver & kidney

Diagnosis

Polycythemia (Rubra) Vera (PRV)

Clinical:

Headaches

Itch particularly after a hot bath

Vascular occlusion

Thrombosis in unusual sites

TIA

Stroke

Splenomegaly

C 3


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Case 3

70 year male patient presented to youhas massive splenomegaly, history of

pallor with malaise..this is a CBC for

him:

WBC x 109/L 2.4 [4-11]

Hb g/L 88 [140-180]

MCV fl 85 [80-100]

Platelets x 109/L 60 [150-450]

Neuts x 109/L 1.0 [2-7.5]

Lymphs x 109/L 1.0 [1.5-4]

Monos x 109/L 0.2 [0.2-0.8]Eos x 109/L 0.1 [0-0.7]

Basos x 109/L 0.1 [0-0.1]

DDx: Leukaemia, lymphoma

Metastatic cancer

Chronic infections

TB, radiation

Glaucomatous disorders

Autoimmune disorders

Myelofibrosis

Blood film:

Tear-drop cell (pathognomic)

Leukoerythroblastic

Diagnosis:

Myelofibrosis

Compesation:

Extra medullary haematopoiesis

Hepatosplenomegaly

C 4


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Case 4 Chronic myeloid leukaemia

Increased WBCs

Normal or high RBCs

Increased platlets

With basophilia & eosinophilia

Philadelphia chromosome t(9:22) & BCR-ABL gene

Blood film:

All stages of maturations

Majority are myelocytes & neutrophils Diagnosis

CBC

Documents

7.Hematology Summary