Hematology

Introduction to anemia & data interpretation

What is the definition of anemia?

• Anemia is a clinical state where the hemoglobin, total RBC count or hematocrit is below the normal limit for sex and age

• Consequence of another underlying disease• Decrease in O2 delivery capacity

What factors regulate erythropoiesis?

• Erythropoiesis= RBC formation• Hypoxia= lox O2 more brc neede kidney

secrete erythropoietin Inc. erythropoiesis• Altitude= high altitude inc erythropoietin• Androgen= inc erythropoietin• ERYTHROPOIETIN controls ERYTHROPOIESIS!!!

What is the difference between true & relative anemia?

True Anemia• Decrease in red cell mass• Due to

– Decreased RBC production– Increased RBC destruction– Both simultaneously

Relative Anemia• Increase in plasma volume• Dilution • Seen in pregnancy

– Due to introduction of iv fluids

What do each of the following measure? Which type of anemia show the results below?

MCV raised• Macrocytic

– Megaloblastic anemia– B12 deficiency– Folic acid deficiency

MCH & MCHC decreased• Microcytic hypochromic

– Iron deciriency– Thalassaemia– Chronic renal failure– Sideroblastic anemia

Give 2 examples of normocytic and normochromic anaemia

• Normocytic= rbc normal size• Normochromic= normal rbc color• Normocytic normochromic anemia= anemia

with normal rbc size and color– MCH & MCV normal

• Hemolysis, Acute blood loss, Marrow infiltration

Nutritional deficiency anemia

What is needed for the transport of iron in the blood? What is needed for the absorption of vit. B12?

• Iron– Transferrion for transport

• B12– Intrinsic factor + transcobalamin II

What are the causes of iron deficiency anemia? Name two.

• Chronic blood loss• GI bleeding: most common anemia cause worldwide• Poor diet intake• Malabsorption

– Gastric resection– Pancreatic insuffiency– GIT infection– Crohon’s disease– Short bowel syndrome

• Menstruation• Childbirth• Pulmonary: haemoptysis• Urinary: renal disease• Rapid growth with insuffiecient Fe: premature infants, children, teenagers• Pregnancy• Lactation

What is the aetiology of megaloblastic anaemia?

• Megaloblastic anemia

• Deficiency of cobalamin (vit B12) and/or Folate (folic acid)

What is pernicious anaemia? What is the main morphological change seen?

What complication is seen in vit. B12 deficiency and not in folate deficiency?

Blood, blood products & transfusion service

What are the major blood groups

Match the following RBC antigens with the appropriate added sugars

Antigen Sugar Added

O

A

B

AB

What does Fresh Frozen Plasma contain? Give 3 conditions where FFP is used

Match the following to their appropriate uses.

Blood Product Uses

A. Whole Blood Liver failure, vit. K deficiency, warfarin overdose

B. Packed Cells Chronic anemia, thalassemia

C. Cryoprecipitate Von Willebrand disease

D. Cryosupernatant Blood volume replacement, exchange transfusion

What are donated blood tested for?

How is ABO cell grouping done?

How is ABO serum grouping done?

List 3 possible agents of transmission of infection by transfused blood.

Hemostasis and bleeding disorders

Name the steps in hemostasis

What are the 2 main functions of thrombin?

Name the Coagulation factorsCoagulation factor Name

I

II

III

IV

V

VII

VIII

IX

X

XI

XII

XIII

What is hemophilia A & ? Give a characteristic sign of hemophilia.

What is von Willebrand disease?

List 3 causes of thrombocytopenia

Give 2 causes of Disseminated Intravascular Coagulation? What are the effects of IDC?

List 2 screening tests for vascular and platelet disorders

List 3 screening tests for coagulation disorders

What is Prothrombin time? What deficiencies can it detect?

What is partial thromboplastin time? What deficiencies can it detect?

What is thrombin time?

Hematinics

Name 4 substances that chelate with iron

State 4 ways iron can be lost from the body

How is iron poisoning treated?

Fill in the blanks about vit. B12Absorbed complexed with…

Location of absorption…

Bound in plasma with…

Deficiency in…

Thalassemia

B-thalassemia is cause by mutations in the genes of the affected individuals. Name one type of gene mutation that can lead to b-

thalassemia.

Regarding b-thalassemia: explain why the red blood cells are hypochromatic

Explain why the rbc have a chortened life span

State 3 clinical features b-thalassemia. Explain why iron overlaod may occur in b-thalassemia patients.

Gice 2 investigations and their expected findings for patients with b-thalassemia.

State 2 common forms of treatment for b-thalassemia

Deletions of the a-globin gene loci result in a-thalassemia. State the number of a-globin genes deleted in the following conditions:

Silent carrier state

A-thalassemia trait

HbH

HbBart

Explain how fetal death due to hydrops fetalis occurs

Chronic fatigue syndrome

True/ false

• Patients with CFS suffer severe fatigue that can be reduced with sufficient rest

• Disturbed sleep, muscle pain, & impaired memory are among the diagnostic criteria for CFS

• Anti-depressant & anxiolytic agents are among the medication treatment for CFS

• Cognitive behavioural therapy can be used to cure patients with CFS

• A doctor can facilitate the treatment outcome of CFS by being empathetic to the patient and educate them about this condition

Aplastic anemia

Describe the morphology of the bone marrow in a patient with aplastic anemia

Give 3 possible causes of aplastic anemia

Give 2 medical treatment for aplastic anemia

What occurs during myelodysplastic syndromes & what medical condition can it predispose to?

Hemoglobinopathies

State the pathogenesis of sickle cell anemia. Include the changes that happen to the haemoglobin and blood flow in response to

low oxygen

State 3 factors that affect RBC sickling

What are the main consequences of HbS

What are the 3 main characteristics of Sickle cell anemia?

Is x-ray important for the diagnosis of sickle cell anemia?

State the 3 morphologies of organs found in sickle cell anemia

State 5 clinical signs and symptoms in sickle cell anemia

Explain why is there autosplenectomy

What are the complications in Sickle cell anemia? Name 4

State 6 investigations that can be carried out other than RBC smear. Include positive and negative findinds

Why homozygous sickle cell trait is more ganderous that the heterozygous cell trait?

Apart from the patient experiencing tiredness and breathlessness due to anemia, what other clinically important signs and symptoms

that can be picked up?

Why does the sickle cell trait protect against malaria?

Name ove virus that can cause aplastic crisis in sickle cell anemia

Haemopoiesis II

Name 3 chemicals that influence platelet production and elaborate on how each chemical affects platelet production

Explain the development steps of granulocyte cells

What are the differences between granulocytes and agranulocytes?

Name 2 chemmicals that control the development of granulocytes

In which from do monocytes appear in bone marrow and in the periphery

In which form are neutrophil granulocytes seen in the bone marrow and in peripheral blood

Platelet biology and Hemostasis

Name the 3 major steps in hemostasis

Name the 3 functions of platelets

Name 2 substances that is released from the surface endothelium

Name 1 stimulatory substance for each of the following processes

Vasoconstriction

Platelet aggregation

Blood coagulation

Describe the roles of thromboxane A2 and Prostacyclin in the process of platelet aggregation

Name 2 clotting factors for each of the following 3 categories

Contact factors

Vik. K dependant factors

Fibrinogen factors

What are the factors that will trigger the following pathway?

Intrinsic pathway

Extrinsic pathway

Give an example of a prothrombin activator

Name an anti-clotting system and briefly describe its process

Name a fibrinolytic system and briefly describe its process

Abnormalities of haemostasis

Write down the effects of Hemophilia A and von Willebrand Factor deficiency

Hemophilia A Von Willebrand Factor deficiency

Bleeding time

Platelet count

Clotting time

APTT

Prothrombin time

What are the 2 functions of the von Willebrand factor?

Define the following temrBleeding time

Clotting time

Plateled count

Prothrombin time

Thrombin time

Activated Partial

Hemolytic Anemia

A young boy, aged 6, was admitted into the hospital for lethargy. The doctor who examined him found the patient to be slightly jaundiced and pale. Splenomegaly was also present. The following are a few of the test

results:

• Peripheral blood smear: microcytic, hyperchromic RBCs. Presence of spherocytes•Reticulocyte count: increased•Plasma bilirubin: increased•Mean cell hemoglobin concentration: inceased

On further questioning, the doctor discovered that the boy’s uncle and two other cousings also had the same condition.

The doctor later concluded that the boy has hereditary spherocytosis

Name another important test which is used to diagnose the pathology. What would the results be if the person has

such condition, and what would you say?

The following statements make up the pathogenesis of hereditary spherocytosis. Arrange them in the proper chronological order.

The cells assume the smallest possible diameter for a given volume. They become spheres

Mutations in the ankyrin molecule cause a secondary deficiency of spectrin, which results in reduced membrane stability of the red blood cells

The affected cells consequently lose membrane fragments as they are exposed to the sheer stresses in the blood circulation

The spherocytes are later sequestered in the sleen and phagocytosed by splenic macrophages. Haemolytic anaemia occurs

“Splenomegaly was also present” how did this happen?

In terms of treatment for hereditary spherocytosis, splenectomy is done when there is a markedly enlarged spleen, severe anemia or complications such as gall stone formation. Then why is such treatment usually delayed

in patients below 5 years old?

Give 2 features seen on peripheral blood smears in hereditary spherocytosis

Match the answers given to the following statements. The answers can be used more than once or none at all

No. Statement Ans.I Only form of haemolytic anemia that results from an acquired membrane defect

secondary to mutation involving the phosphatidyl inositol glycan A (PIG-A) gene which affects myeloid stem cells

Ii Asymptomatic unless RBCs are subjected to oxidant injury by exposure to certain drugs, toxins or infections

Iii Schistocytes (made up of Burr cells, Helmet cells, triangle cells, microspherocytes) seen on peripheral blood smears

Iv Heinz bodies and “bite” cells

v Only disease associated with increased mean cell hemoglobin concentration (MCHC)

vi Desttruction of RBCs within cells of mononuclear phagocyte system (MPS)

A: G6PD def. B: Extravascular hemolysis C: Hereditary spherocytosis D: Paroxysmal nocturnal hemoglobinuria E: Intravascular hemolysis F: hemolytic anemia

Both intravascular and extravascular hemolysis occur in G6PD dieficiency. List 2 differences between intravascular and extravascular hemolysis

Intravascular hemolysis Extravascular hemolysis

Why are the serum haploglobin level characteristically low in hemolytic anemia?

Why would G6PD def. lead to hemolytic anemia?

Plasma cell Dyscriasis

A 45 year old man went to a hospital yesterday after he fell down in the park while taking his dog out for a walk. When examined, his right leg was a little swollen and quite tender.The patients also noted that he gets tires easily in the last 3 months. He can no longer play badminton continuously with his friends, not swin 40 laps like he used to. He also tends to bruise easily, and suffers from excruciating bond pains.A number of investigations were carried out:

•X-ray of the right leg: numerous bone lesions noted•Urine test: presence of Bence-jones proteins•Serum electrophoresis: “M” spike absent•Calcium levels in serum: elevated•Peripheral blood smear: Normocytic, normochromic anemia. There is rouleaux formation•Bone marrow aspiration: increased numbers of plasma cells

• What is your probably diagnosis?• What is bence-jones proteins?• Why is the “M” spike not present in this case?

Give 3 complications of this medical condition

Match the following with the most appropriate answers

No. Statements Ans.

i This is used to stage multiple myeloma and determine prognosis

ii Presence of M proteins in serum of asymptomatic, healthy people

iii Precipitation of macroglobulins at low temperaturm, producing Reynaud’s phenomenon and cold urticaria

iv X-rays show characteristic soap-bubble/ pepper-pot appearance

v Found in the upper respiratory tract in 80% cases

vi Mott cells and Russell bodies present

A: Cryiglobulinaemia B: Durie-Salmon staging system C: Monoclonal gammopathy of uncertain significance D: Multiple myeloma E: Extramedullary plasmacytoma F: Rai’s Staging System G: Waldestorm Macoglobulinaemia

Leukocyte abnormalities and their benign disorders

Where is the highest concentration of bone marrow found?

What is the peripheral leukocyte count influenced by?

What is the contrasting feature of a leukaemoid reaction compared with chronic myeloid leukaemia?

Name 5 drugs that induce neutropenia

What are 2 mechanisms that lead to neutropenia?

Acute & Chronic Leukemia

Regarding chronic leukemia

• The indolent and low grade quality of most chronic leukemias allow time to achieve cures with appropriate therapy

• Many cases exhibit specific chromosome abnormalities• Chronic myelogenous leukemia almost always

progresses to an acute leukemia• Chronic lymphocytic leukemia is generally a neoplasm

of B lymphocytes• Chronic leukemias are proliferations or accumulations

of mature or differentiated cells

Regarding leukemias

• The Philadelphia chromosome can be onserved in CML and ALL

• The poorest prognosis for patients with CLL is associated with anemia and thrombocytopenia

• In hairy cell leukemia, there will be pancytopenia, splenomegaly, and clonal proliferation of b lymphoid cells

• There will be positive tartrate resistnace and phosphate test in AML

• Serum vitamin b12 level measurement can be used to differentiate AML & ALL

Lymphoma

State 2 macroscopic appearances of the affected lymph nodes in Hodgkin’s disease

What is specific name for the true neoplastic cell seen in Hidgkin disease? Describe how it looks like

Name the 2 types of Burkitt Lymphoma and give 2 differences between them

How does non-hidgkins lymphoma spread?

Give 2 clinical features of Non-hodgkins lymphoma

Between hidgkins and non-hidgkins lymphoma, in which is staging a useful guide to therapy?

State two viruses that can be etiological agent in lymphoma

Myeloproliferative Disorders

Define myeloproliferative disorders

What characterizes the spent phase?

IN polycythemia vera, what characteristic of its progenitor cells may be a possible explaintation for the increased production and

proliferation?

Polycythemia vera can transform to a type of leukemia. Which type is it?

State 2 clinical features of polycythemia vera

Insert the appropriate alphabet

Marked increase in marrow reticulin fibersMarked splenomegaly

Normochromic normocytic anemia

Increased tendency towards peptic ulcers

Minimal reticulin fibrils

Trephine biopsy to establish the diagnsosisAlkaline phosphatase levels are above normalTear drop cells

A: polycythemia vera B: essential thrombocytosis C: myelofibrosis

Principles of anticoagulant therapy

Vitamin K is an important co-factr in the formation of clotting factors II, VII, IX, and X. Warfarin is an anticoagulant which is very similar in structure to

vit. K. Explain how warfarin functions as an anticoagulant

Heparin is a commonly used parenteral anticoagulant. Describe its functions

Give 2 examples of antiplatelet agents and briefly describe their function

What are the 3 major categories of drugs used to prevent hemostasis

Briefly describe the workings of the fibrinolytic system

Malaria

Name 2 stages of the malaria parasite’s like cycle in the mosquito

Hypnozoites are dormant malaria parasites in the liver. Name one species of malaria parasite which may result in hypnozoite

production

Give 2 clinical signs/ symptoms of malaria

List 3 complications of malaria

Malaria parasites may be eradicated with drugs during certain stages in their life cycles. Name 2 drugs used to treat malaria

Babesiosis & Trypanosomiasis

Give a causative agent of babesiosis

Give 2 morphological differences between the causative agents of babesiosis and malaria

Which parasite is transmitted by the tick, Ixodes scapularis

Which parasite usually causes babesiosis in asplenic patients?

What is the infective stage of the causative organism of African trypanosomiasis

Give an investigative technique used in the diagnosis of African trypanosomiasis

What is the vector for American trypanosomiasis?

State a complication of Chagas disease

What is the treatment for Chagas disease

Viral hemolytic diseases

Explain the pathophysiology of shock in dengue fever

Describe the problem with developing a vaccine for dengue hemorrhagic fever

Give one preventive measure that can be taken against dengue hemorrhagic fever directed against the vector and disrupting its

life cycle

What is the vector for the sylvatic (jungle) yellow fever?

State one mode of transmission of the causative agent of Rift Valley Fever

Give the reservoir and mode of transmission for Lassa fever

List 2 parasites that cause lympathic filariasis

Give a brief explaination on the life cycle of a lympathic filariasis parasite

Give 2 drugs that are used to trat lympathic filariasis

What is the main vector for onchocerciasis

If a patient is suspected of having onchocerciasis, what would be the clinical presentations that you would expect to find in this

patient? Give 3

List a method of control of onchocerciasis

Epidemiology of zoonoses and vector-borne diseases

Match the following features of disease to the correct causative disease. The diseases given can be used once, more than once or not at all.

Features of disease Disease

Acute inflammatory vial disease of the brain, spinal cord & meningesAlso known as the “sleeping sickness”

The anopheles mosquito is a vector

Vector is the tromboculid mite

Vector is the Tsettse fly

Transmitted through the bite of sandflies. Causes disfiguration and ulceration of the human host

Japanese Encephalitis Trypanosomiasis Malaria Scrub TyphusLeishmaniasis Filariasis Plague Yellow fever

Give simple explainations on what the following terms mean

Disease vector

Animal reservoir

Disease carrier