Summary of all hematopoietic

pathology lectures

By: MMH
 ⬇
⬆ ⬇ ⬆ ⬇
Aplastic anemia
– Normochromic normocyric
– Pancytopenia in peripheral blood
– Hypoplastic (hypocellular) bone marrow
– Mostly cause is unknown but an autoimmune mechanism appears to be important.
– No organomegally
– No abnormal cells can be seen in the peripheral blood

IDA
– Hypochromic microcytic
– Most common cause of anemia
– Increasing of iron absorption (in duodenum) from 5-10% to 20-30%
– Ferrous iron Fe+2 is iron used in transportation, but Ferric iron Fe+3 in Hb iron.
– Blood lose in most common cause of IDA.
– Reticulocyte
– Platelets
– serum iron, serum ferritin, TIBC

Megaloblastic anemia
– Macrocytic normochromic
– Hypersegmented neutrophils
– Hypercellular BM
– impaired DNA synthesis, due to Vitamin B12(cobalamin) or B9(folate) deficiencies or
interference with DNA synthesis by other mechanisms
– Cobalamine is absorbed in ileum (intrinsic factor dependent) and has 3 forms,
methylcobalamin, Deoxyadenosylcobalamin and Hydroxocobalamin
– B12 caused by impaired absorption or reduced intake
– B9 caused by impaired absorption, reduced intake, excess utilization and drugs
– leukocytes
– Thrombocytopenia
– Anisocytosis poikilocytosis, macrocytosis, tear drop cells
– Neuropathy and psychiatric problems in B12
– Sterility
HEMOLYTIC ANAEMIAS
– increase in the rate of the red cell destruction
– Normochromic normocytic
– May be extra vascular or intravascular
– Reticulocytes in blood
– Erythroid hyperplasia – BM
– Can be heredatory: membrane defect (hereditary spherocytosis -spectrin defect-, hereditary
elliptocytosis) or defect in metabolism (G6PD deficiency) or Genetic defect of
hemoglobin( thalassemia, sickle cell anemia)
– Or can be aquired: immune (either auto immune - Cold or warm- or alloimmune), drug
associated…etc

Hemoglobinopathies:
Thalassemia
– Hypochromic microcytic anaemia
– reduced rate of synthesis of α or β globin chains.
– autosomal recessive
– Can be major, intermedia or minor
– β thalassemia caused by a point mutation on Ch. 11
– Extramedullary hemopoiesis & iron overload
– Intense marrow hyperplasia
– Repeated blood transfusion lead to multiple organ failure & death ( th. Major)
– reticulocyte
– Anisocytosis and poikilocytosis mainly target cells
– α-Thalassemia caused by gene deletion:
● --/-- —> hydros fetalis (Hb barts)
● --/-α —> HbH
● --/αα —> α th. Minor
● -α/αα —> silent
Sickle cell anemia: ( Hb-α2βs2)
– By replacement of valine by new glutamic acid on Ch. 6 on β chain
– Crisis: Painful vascular – occlusive crisis, Vascular sequestration crisis, Aplastic crisis and
Haemolytic crisis
G6PD Deficiency
– G6PD —> GSH —> oxidative stress —> RBC Distraction
– Extravascular hemolysis
– Heinz body formation
– X-linked
– M>F
– 5 classes, 1 is most severe and 5 is mildest
– Spleenomegaly, dark urine, fatigue, SOB, pallor
– Bite cells*, cluster cells, Heinz bodies

MPNs (clonal stem cell disorders)

PV:
● erythropoietin
● Hb, Hct
● Blood hyper-viscosity
● platelet and neutrophils
● NAP score
● serum uric acid
● Hypercellular bone marrow
● uncleared RBCs
● In secondary polycythemia erythropoietin decrease

ET
– Megakaryocitin clonal lineage
– thrombocytes and megakaryocytes in BM

MF
– Bone marrow fibrosis
– Extramedullary erythropoiesis —> tear drop cells
– Anemia
– Leukoerythroblastic blood film
– NAP score
– Serum uric acid & LDH levels
 – Serum uric acid & LDH levels

CML
– abnormality marked proliferation of mature and maturing granulocytes.
– Male predominance
– Most common adult leukemia in western world
– Philadelphia Ch. Translocation (t9;22), which chromosome 22 is abnormal, is diagnostic for
CML

Multiple Myeloma
– plasma cell accumulation in the bone marrow
– Monoclonal protein present in serum or urine or both and is diagnostic for MM
– Most of cases are asymptomatic or smouldering myeloma
– Only 10% is symptomatic and need therapy
– CRAB and recurrent infections are symptomatic MM’s associated symptoms
– Blood Hyperviscosity (like polycythemia Vera)
– May there is normochromic normocytic or macrocytic anaemia
– Rouleaux formation is marked in many cases.
– serum albumin
– LDH
– serum creatinine
– serum calcium

Other plasma cell neoplasms:

1. Solitary plasmocytoma: These are isolated plasma cell neoplasms, usually involving bones or
soft tissue such as the mucosa of the upper respiratory and gastrointestinal tracts or the
skin. My not become myeloma
2. Plasma cell leukemia: is characterized by a high number of circulating malignant plasma cells.
The features are a combination of acute leukaemia and myeloma
3. MGUS: A persistent serum paraprotein may be sometimes be detected without any evidence
of myeloma or other underlying disease
Leukemia
– Cancer of the blood cells
– Acute or chronic
– Acute leukemia (myeloid & lymphoblastic): blasts > 20%
– Diagnosis: anemia, infection, bleeding, tissue infiltration & (Hb, WBC, Plt) & other special
tests
AML:
– Adult leukemia, rare in children
– Classified From M0 to M7
– Gum hypertrophy (M4)
– Hepatosplenomegaly
– DIC (M3) —> t(8:21), t(15:17)
ALL:
– Most Common In children (2-10 years) 3*
– Has L1, L2 and L3
– L3 —> t(8:14)
CLL:
– More common than CML
– WBC
– Anemia, in later stages
– thrombocytepenia May occur
– Smudge or smear (damaged) cells
– In Immunophenotyping shows that the lymphocyte are B cells (CD19)

Lymphoma
– cancer of the lymph nodes and the lymphatic tissues of the body
– Features are six P’s: PAINLESS, PALPABLE, PERSISTENT, PERIPHERAL, PROGRESSIVE,
POLYLYMPHADENOPATHY
– 2 groups: Hodgkin Lymphomas & Non-Hodgkin Lymphomas (NHL)
Hodgkin’s lymphoma:
– M>F
– EBV, HIV
– Characterized by presence of Reed-Sternberg cells
– Multinucleated giant cells
 – enlarged nodes are usually peripheral and may be seen in one or both sides of the neck, in
the axillae or in the inguinal or femoral regions.
– Normochromic normocytic anemia is most common
– Bone marrow involvement is unusual in early disease, may be in advance stages
– If lead to leukoerythroblastic picture, neutrophilia and eosinophilia are frequent
– ESR & CRP are raised
– Serum lactate dehydrogenase (LDH) raised
– Classifications:
A. Lymphoblastic predominance: nodal architecture is lost, Reed-Sternberg cells (RSC) are scanty.
B. Nodular sclerosis: characterized by the replacement of the lymph node parenchyma by
interconnecting bands of collagenous
C. Mixed cellularity: Reed- Sternberg cells are more numerous and the stroma shows a mixture of
neutrophils, normal histiocytes, plasma cells, lymphocytes, eosinophils and fibroblasts.
D. Lymphocyte depleted: there is a paucity of lymphocytes and an abundance of Reed-Sternberg
cells in this group.
– Has staging from l to V

Non-Hodgkin’s lymphoma:
– most commonly of B-cell origin
– Divided to low grade (relatively indolent, but are very difficult to cure) and high grade
(aggressive and need urgent treatment but are often curable) lymphomas
– AIHA
– Serum LDH is raised
– Low grade: follicular lymphoma - t(14;18) -
– High grade: burkitt’s - t(2;8), t(8;22), t(8;14)
– T Cell NHL’s: Mycosis fungoides, Sezary syndrome

Bleeding disorders
– Primary hemostatic disorders: vascular defects & platelet low or defects
– Secondary hemostatic disorders: coagulation defects
Vascular abnormalities:
Inherited:
● hereditary hemorrhagic talengactasia
● Ehlers-danlos syndrome
Aquired:
● Senile purpura
● Vit. C deficiency
● Steroid purpura
● Henoch-schonlein purpura (IgA mediated)

Platelet abnormalities:
—> low plt. count (thrombocytopenia)
—> platelet dysfunction (thrombocytopathy)
– they’re characterized by spontaneous skin purpura, mucosal hemorrhage and prolonged
bleeding after trauma
Thrombocytopenia: —
1—> production failure
1. Drugs (heparin)
2. Aplastic anemia
3. Leukemias
4. Megaloblastic anemia
5. Cancers

2—> consumption
1. Immune
2. DIC
3. TTP

3—> Spleenic pooling

Thromocytopathies:—

1—>inhireted:
● Glanzmans disease:
– Absence of llb/llla
– Defect in platelet aggregation and normal morphology

2—>aquired:
● NSAIDs —> inhibit COX2 —> thromboxane A2 —> plt. aggregation inhibition
 ● Multiple myeloma

Normal bleeding time 2-5 mins

Coagulation factor disorders:—

—>inhireted: —> aquired

1. Hemophilia A & B 1. Liver disease & Vit. K deficiency
2. vWdisease 2. Heparin & warfarin over dose
3. DIC
Inhireted
Hemophilia A:
– Factor Vll deficiency (M>F)
– Hemarthrosis
– X-Linked recessive
– 3 severities ( mild, moderate and severe)
– Only aPPT —> Prolonged
– Anemia —> IDA due to bleeding
Hemophilia B: Factor lX deficiency —> also called Christmas disease

vonWillebrand’s disease:
– deficiency in vWfactor
– Autosomal dominant

Acquired
Vit. K deficiency
– needed for synthesis: factors ll, VII, IX, X and protein C and S
– Both PT and aPPT are prolonged

Overdose of Anticoagulant therapy

● Heparin:
– Injectable bcz not absorbed by GIT
– Prolonged aPPT
– Profaning sulfate is antidote
 ● Warfarin:
– Oral
– Prolonged PT
– Antagonize Vit. K

DIC
– Due to wide spread activation of the coagulation factors in the blood stream, so there is
consumption of the coagulation factors and platelets.
– widespread deposition of fibrin with activation of the fibrinolytic system.
– All PT, aPPT and TT are prolonged
– Decrease fibrinolysis
– platelets

Normal value Prolonged in

Prothrombin time 10-15 seconds Liver disease,
(PT) Warfarin therapy, Vit.
K deficiency, DIC
aPPT 25-40 seconds Hemophilia, heparin
therapy, liver
disease, Vit. K
deficiency, DIC.
TT 9-13 seconds DIC, Heparin therapy
– PT measures effectiveness of extrinsic pathway
– aPPT measures effectiveness of intrinsic pathway
– TT measures time for thrombin to convert fibrinogen —> fibrin

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