Kumar and Clark Haematology Flashcards
What are the lifespans of blood cells
RBC= 120
Platelets = 7 days
Granulocytes = 7 hours.
production sites of T and B cells
T= Thymus
B= Bone marrow
Where is Thrombopethin produced ?
kidneys, liver and certain bone marrow stromal cells
What is the use of granulocyte-colony-stimulating factor (G-CSF)?
To accelerate haemopoietic recovery after chemotherapy and haemopoietic cell transplantation
What is the use of erythropoethin ?
It is used to treat anaemia in patients with chronic kidney disease and in patients with certain blood cancers.
What is the use of thrombopoietin receptor agonists such as Romiplostim?
To treat immune thrombocytopenic purpura.
What is RDW?
It s a measure of the variability in size of red blood cells. An elevated RDW suggests increased variation in red cell size – that is, anisocytosis – and this is seen in iron deficiency.
What is ESR?
It is the rate of fall of red cells in a column of blood and is a measure of the acute-phase response.
What does an elevated ESR indicates ?
It reflects an increase in the plasma concentration of large proteins, such as fibrinogen and immunoglobulins. These proteins cause rouleaux formation which causes red cells clumping together and therefore falling more rapidly.
What are CRPs ?
It is a protein produced in the acute-phase response. It is synthesized exclusively in the liver and rises within 6hours of an acute event.
What are the signs of anaemia ?
- Pallor.
- Tachycardia.
- Systolic flow murmur.
- Cardiac failure.
Koilonychia is pathognomonic for what type of anaemia ?
Chronic iron deficiency anaemia.
Jaundice found in what type of anaemia
Hemolytic anaemia
Bone deformities found in what type of anaemia ?
Thalassaemia major
Leg ulcer occur in what type of anaemia ?
Sickle cell anaemia.
What are the peripheral blood investigations in Anaemia ?
- red cell indices
- WCC
- platelet count
- reticulocyte count (as this indicates marrow activity)
- blood film, as abnormal red cell morphology may indicate the diagnosis.
Dry bone marrow tap indicates ?
Myelofibrosis or aplastic anaemia
What are the causes of microcytic hypochromic anaemia?
- Iron deficiency
- defect in globin production such as thalassaemias.
- defect in haem synthesis, termed sideroblastic anaemia.
- Chronic anaemia of chronic disease.
What are the causes of iron deficiency anaemia ?
- blood loss
- increased demands, e.g. growth and pregnancy
- decreased absorption (e.g. post-gastrectomy)
- poor intake.
what are the symptoms of chronic Iron deficiency anaemia ?
- brittle nails
- spoon-shaped nails (koilonychia)
- atrophy of the papillae of the tongue
- angular stomatitis
- brittle hair
- Plummor-Vinson syndrome.
What is the clinical picture of Iron deficiency anaemia ?
MCV <80
MCH < 27 pg
Anisopoikilocytosis
Serum Iron and ferritin decreased
Serum TIBC increased
Iron in marrow and erythroblasts are absent.
Why is ferritin sometimes elevated in Iron deficiency anaemia ?
It is an acute phase reactant. Therefore, it may be elevated in the presence of inflammatory or malignant diseases and also in the presence of liver damage
What is the utility of serum soluble transferrin receptors in anaemia.
The number of transferrin receptors released into the serum from bone marrow erythroblasts increases in iron deficiency. It will help to differentiate between iron deficiency anaemia and anaemia of chronic disease in which it is low.
What is the approximate time it takes to replenish iron stores and low haemoglobin ?
6 moths
What is the pathophysiology of anaemia of chronic disease ?
It is the most common type of anaemia in hospitalised patients and in patients with chronic diseases.
The pathophysiology consist of Low iron release from bone marrow to developing erythroblasts and inadequate EPO response to anaemia + high hepcidin levels -> Low red cell survival > Low TIBC, normal or increased ferritin.
What is a novel marker to differentiate iron deficiency anaemia from anaemia of chronic disease
Serum hepcedin levels as they are normal or decreased in Iron deficiency anaemia and increased i anaemia of chronic disease.
What is the cause of vast majority sedorrhoblastic anaemia in adults ?
primary acquired sideroblastic anaemia: a myelodysplastic syndrome.
acquired causes of sedorrhoblastic anaemia ?
- Isoneazide,
- alcohol
- Led toxicity.
What are the causes of normocytic, normochromic anaemias?
- acute blood loss
- endocrine disorders: hypopituitarism, hypothyroidism and hypoadrenalism.
- haematological disorders: aplastic anaemia and some haemolytic anaemias.
What are Macrocytic Megaloblastic anaemia?
Megaloblastic anaemia is characterized by the presence in the bone marrow of erythroblasts with delayed nuclear maturation because of defective DNA synthesis ( Megaloblasts).
What are the causes Macrocytic Megaloblastic anaemia?
-B12 deficiency or metabolism defects.
- Folic acid deficiency or metabolism defects.
- congenital enzyme deficiencies in DNA synthesis (e.g. orotic aciduria)
- drugs interfering with DNA synthesis: hydroxycarbamide (hydroxyurea), azathioprine
-myelodysplasia due to dyserythropoiesis.
Laboratory findings in Macrocytic Megaloblastic anaemia?
High MCV
Peripheral blood smear shows oval macrocytes + multilobbed polymorphs.
- If severe, there may be leucopenia and thrombocytopenia.
- LDH is typically elevated reflecting ineffective erythropoiesis.
What are the causes of B12 deficiency?
Low dietary intake
* Veganism
Impaired absorption
Stomach
* Pernicious anaemia
* Gastrectomy
* Congenital deficiency of intrinsic factor
Small bowel
* Ileal disease or resection
* Bacterial overgrowth
* Tropical sprue
* Fish tapeworm ( Diphyllobothrium latum )
Abnormal utilization
* Congenital transcobalamin II deficiency
* Nitrous oxide (inactivates B 12 )
What is pernicious anaemia ?
Pernicious anaemia (PA) is an autoimmune disorder in which there is atrophic gastritis with loss of parietal cells in the gastric mucosa and consequent failure of intrinsic factor production and vitamin B 12 malabsorption.
What is the Tx of B12 deficency ?
Hydroxocobalamin 1000 μg can be given intramuscularly to a total of 5–6 mg over the course of 2weeks; 1000 μg is then necessary every 3months for the rest of the patient’s life.
What are the causes Macrocytosis without megaloblastic changes?
- alcohol excess
- liver disease
- reticulocytosis (e.g. due to haemolysis)
- hypothyroidism
- some haematological disorders (e.g. aplastic anaemia, myelodysplasia, pure red cell aplasia, multiple myeloma)
- drugs (e.g. hydroxycarbamide, azathioprine)
- cold agglutinins due to autoagglutination of red cells
What is the definition of aplastic anaemia ?
Aplastic anaemia is defined as pancytopenia with hypocellularity (aplasia) of the bone marrow; there are no leukaemic, cancerous or other abnormal cells in the peripheral blood or bone marrow.
What are the labs in aplastic anaemia ?
- Pancytopenia.
- The virtual absence of reticulocytes.
- A hypocellular or aplastic bone marrow with increased fat spaces
Epidemiology of Hereditary spherocytosis?
Hereditary spherocytosis (HS) is the most common inherited haemolytic anaemia in Northern Europeans. It can be inherited in an autosomal dominant or recessive manner, but in some patients occurs by spontaneous ( de novo ) mutation
What is the clinical presentation in Hereditary spherocytosis?
- may present with jaundice at birth
-The patient may be asymptomatic at birth and later on may develop anaemia, gallstones, splenomegaly or, rarely, ulcers on the leg.
-the course of the disease may be interrupted by aplastic, haemolytic and megaloblastic crises
-Chronic haemolysis leads to the formation of pigment gallstones
What are the laboratory findings in Hereditary spherocytosis ?
- Mild to severe anaemia
-spherocytes and polychromasia - Hemolysis
- Positive osmotic fragility test
- Negative direct coomb test.
What are the three main types of Hereditary hemolytic syndromes ?
Hereditary spherocytosis
Hereditary elliptocytosis
Hereditary stomatocytosis
What are the chains of Foetal Hb ?
two α and two γ chains
What are quantitative disorders of haemoglobin ?
Disorders marked by reduced globin chain production example: thalassaemia.
what are qualitative disorders of Hb?
These are structural abnormalities of Hb such as sickle cell disease.
What is the management of beta thalasemia major and intermediate or Transfusion dependent thalasemia ?
- Life long folic acid supplementation.
- Regular transfusions should be given to keep the haemoglobin above 100 g/L. Blood transfusions may be required every 4–6 weeks.
- Desferrioxamine + Vitamin C for transfusion haemosiderosis (iron overload).
-BMT from HLA matched donners.
What is sickle cell disease ?
Sickle cell haemoglobin (HbS) results from a single-base mutation of adenine to thymine, which produces a substitution of valine for glutamic acid at the sixth codon of the β-globin chain (α 2 β 2 6glu→val )
What is the pathogenesis of sickle cell disease ?
Deoxygenated HbS molecules are insoluble and polymerize. The flexibility of the cells is decreased, and they become rigid and take up their characteristic sickle appearance . It is initially revisable, but later on becomes irreviable.
What are the clinical features of sickle cell anaemia ?
1) Vaso-occlusive crises: dactylitis
2) Acute chest syndrome: This occurs in up to 30%, and pulmonary hypertension and chronic lung disease are the most common causes of death in adults with sickle cell disease.
3) Anaemia
Chronic haemolysis produces a stable haemoglobin level, usually in the 60–80 g/L range, but an acute fall in haemoglobin can occur owing to:
* splenic sequestration
* bone marrow aplasia
* further haemolysis due to drugs, acute infection or associated glucose-6-phosphate dehydrogenase (G6PD) deficiency.
What is the blood count pattern in sickle cell disease ?
The level of haemoglobin is in the 60–80 g/L range, with a high reticulocyte count (10–20%)
What is the gold standard test for sickle cell disease?
Haemoglobin electrophoresis
What drug can be used in increase HbF in sickle cell disease ?
hydroxycarbamide
What are the metabolic disorders of Hb ?
- G6PD deficiency
- Pyruvate kinase deficiency
- Pyrimidine 5′ nucleotidase deficiency
What is the test to identify AHA ?
Positive direct antiglobulin (Coombs’) test
What are the types of AHA ?
warm’ (65%), ‘cold’ (30%) and mixed (5%)
what is warm AHA ?
IgG antibodies predominate and the direct antiglobulin test ( Coomb’s test)is positive with IgG alone, IgG and complement, or complement only
What is the cold AHA ?
It is charecterized by IGM and C3d.
What type of hemolysis is seen in Paroxysmal nocturnal haemoglobinuria?
Intravascular.
What is the function of Antithrobin III?
inhibit Factor IIa,IXa, Xa, XIa, XIIa. Antithrobin 3 deficiency will cause Hypercoagulable state leading to venous or arterial thrombosis.
Anti-Thrombin III is required for what drug to work ?
Heparin. Deficiency causes Heparin insensitivity.
What is the effect of splenectomy on red cell morphology ?
The most prominent changes and include Howell–Jolly bodies (contain basophilic nuclear remnants), Pappenheimer bodies (contain sideroblastic granules).
What is the diagnostic test for Antithrombin III deficiency ?
Antithrombin- Heparin cofactor assay.
How to interpret PT ?
The PT measures factors VII, X, V, prothrombin and fibrinogen: the classic ‘extrinsic’ pathway and is prolonged if any of these factors is low.
When is PT is called INR ( patient PT/ Control PT) ?
During Warfarin therapy monitoring.
How to interpret aPTT?
The APTT measures factors XII, XI, IX, VIII, X, V, prothrombin and fibrinogen (the classic ‘intrinsic’ pathway), and is prolonged in deficiencies of one or more of these factors
What are the causes of Thrombin time prolongation?
- fibrinogen deficiency
- in qualitative defects of fibrinogen (dysfibrinogenaemia)
-inhibitors such as heparin or FDPs
DX criteria for anti-phospholipid syndrome?
DVT or Presence of pregnancy complications + Anticardiolipin antibody or Lupus antibody or Anti-beta 2 Glycoprotein antibody.
What are vascular disorders
They are characterized by easy bruising and bleeding into the skin. Bleeding from mucous membranes sometimes occurs but the bleeding is rarely severe. Laboratory investigations, including the bleeding time, are normal.
What are the causes of Thrombocytopenia ?
- impaired production due to Selective megakaryocyte depression.
- bone marrow failure
- Megaloblastic anaemia
- Excessive destruction or increased consumption
- Sequestration
-Dilutional due to Massive transfusion.
What is the only abnormality seen in Immune Thrombocytopenic purpura ?
Thrombocytopenia
What is the treatment for longterm remission of resistant ITP?
Thrombopoietin receptor agonists , such as romiplostim and eltrombopag, which drive increased platelet production.
What is the treatment for refractor ITP?
Splenectomy.
What is Thrombotic thrombocytopenic purpura?
(TTP) is a rare but very serious condition, in which platelet consumption leads to profound thrombocytopenia. There is a characteristic symptom complex of florid purpura, fever, fluctuating cerebral dysfunction and microangiopathic haemolytic anaemia with red cell fragmentation, often accompanied by acute kidney injury.
What is the cause of TTP ?
This occurs due to a reduction in ADAMTS-13
What is the laboratory hallmark of TTP ?
elevated LDH
What is the main stay treatment for TTP?
-Plasma exchange to remove Autoantibodies to ADAMTS13.
- Cryoprecipitate and solvent-detergent FFP both contain ADAMTS-13
- Pulsed intravenous methylprednisolone is given acutely.
- Rituximab is a Tx choice.
What is Hemophelia A ?
This is due to factor VIII deficiency and it is an X linked disorder. Therefore, the son of a female career has 50% chance for hemophelia A and the daughters of the Hemophelic father are all careers.
What are the clinical features of Hemophelia A
The normal level of factor VIII is 50–150 IU/dL:
severe haemophilia: FVIII level < 1 IU/dL.
moderate haemophilia: FVIII level between 1 to 5 IU/dl.
Mild hemophelia: FVIII level > 5 IU/ dl.
What are the laboratory markers of Hemopheila A
an isolated prolongation of the APTT and a reduced level of factor VIII.
What are the Laboratory findings in VWF disease ?
Increased bleeding time + Prolonged aPTT+ decreased VIII-C complex+ reduced VWF.
What are the laboratory findings in Vitamin K deficiency?
Prolonged PT and aPTT
What is the treatment of Hemophelia A ?
Administration of factor VIII concentrate by intravenous infusion to achieve normalization of levels.
Where VWF gene located
chromosome 12.
What is VWFD type 01 ?
It partial quantitative deficiency of VWF; significant type 1 VWD is usually inherited as an autosomal dominant.
- ## Patients have mild clinical features.
What is Type 2 VWFD ?
is due to a qualitative abnormality of VWF; it too is usually inherited as an autosomal dominant. Clinical features are similar to Type 01.
What is Type 03 VWFD?
It is recessively inherited and patients have virtually complete deficiency of VWF. Their parents are often phenotypically normal.
- Clinical features are severe hemarthrosis. It is the severe type.
What is the management of VWFD ?
In type 01 and 02: Desmopressin.
In Type 03: plasma-derived factor VIII concentrates that contain intact VWF are the mainstay of replacement therapy.
What are the physical examination findings in Antiphospholipid syndrome ?
- Livedo reticularis
- Superficial thrombophlebitis
-Leg ulcers
-Painful purpura
-Splinter hemorrhages
Venous thrombosis–related findings in Antiphospholipid syndrome ?
-Leg swelling (DVT)
-Ascites ( Budd-Chiari syndrome)
-Tachypnea (pulmonary embolism)
-Peripheral edema (renal vein thrombosis)
-Abnormal funduscopic examination results (retinal vein thrombosis)
Arterial thrombosis–related findings in Anti-phospholipid syndrome
-Abnormal neurologic examination results (eg, stroke)
-Digital ulcers
-Gangrene of distal extremities
-Signs of myocardial infarction
-Heart murmur (frequently aortic) or -mitral insufficiency ( Libman-Sacks endocarditis)
-Abnormal funduscopic examination results (retinal artery occlusion)
