Haematology Flashcards

1
Q

Describe the general basics of blood compatibility

A

O Groups are universal RBC donors, but can be only be given O RBCs as anti-A and anti-B are present in plasma

A groups have anti-B in plasma, so therefore neither B or AB can be given. They can be given group O or A.

AB can receive any blood group, but cannot be a donor with the exception of plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Management of Blood Transfusion Reactions

A

X

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Blood Transfusion Reactions

A

X

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

RhD Antigen

A
  • RhD _+ve individuals can either be heterozygous (Dd) or homozygous (DD)
  • RhD -ve individuals will be homozygous for dd
  • RhD is immunogenic, so can easily cause sensitisation events
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

RBC Alloantibodies

A

Tend to be IgG antibodies, therefore delayed haemolytic transfusion reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the principles of pre-transfusion testing

A
  • Group & Screen aka Group & Save
  • Identify ABO & RhD Group
  • Ab Screen to detect presence of Abs in plasma to main RBC antigens
  • Electronic if negative Ab Screen
  • Wet if Abs or other concerns
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the indications for Transfusion?

A

Benefits vs. Risk

  • Benefits: Increase O2 Haemoglobin
  • Risks: infection, prion - variant cjd, acute reaction, fluid overload
  • Asymptomatic individuals do not require transfusion unless haemoglobin is very low (<70g/L)
  • NICE Guidelines state transfuse patients with Hb <70g/l, aiming for 70-90g/L
  • If patient is chronically hypoxic or heart issues with anaemia, transfusion may be required at higher haemoglobin
  • Restrictive thresholds can be implemented for individuals with normal bone marrows
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Alpha-1 Anti-trypsin Deficiency

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Causes of Thrombocytopenia

A

Problems with Production

Sepsis

B12 or folic acid deficiency

Liver failure causing reduced thrombopoietin production in the liver

Leukaemia

Myelodysplastic syndrome

Problems with Destruction

Medications (sodium valproate, methotrexate, isotretinoin, antihistamines, proton pump inhibitors)

Alcohol

Immune thrombocytopenic purpura

Thrombotic thrombocytopenic purpura

Heparin-induced thrombocytopenia

Haemolytic-uraemic syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Idiopathic Immune Thrombocytopenia (ITP)

A

E: Commonest form of thrombocytopenia. Older females.

A: Immune-mediated platelet destruction. Following a recent infection (children). Chronic (adults)

C: Purpuric rash, commonly affecting shins. Bleeding (epistaxis)

Ix: Diagnosis of exclusion. Platelets <150. Antiplatelet autoantibodies. BM aspiration (megakaryocytes). NO Schistiocytes.

Tx:

1st Line: Prednisolone (steroids)

IV immunoglobulins (active bleeding/invasive procedure)

Rituximab (a monoclonal antibody against B cells)

Splenectomy (if platelets < 30 after 3 months of steroid therapy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Thrombotic Thrombocytopenic Purpura (TTP)

A

E: Rare.

A: Defect of ADAMS13 protein (responsible for VWF inactivation, thus clotting). VWF overactivity - platelets used up. Results in microangiopathy; blood clots in small vessels.

C: Purpuric rash. Anaemia. Thrombocytopenia. Fever.Nerologicsymptoms (aphasia, diplopia, clumsiness).Renal dysfunction.

Ix: Increased bleeding time. Schistiocytes present on smear.

Tx:

Plasma exchange

Steroids

Rituximab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Heparin Induced Thrombocytopenia (HIT)

A

E:

A: Heparin-induced antibodies target platelets - Platelet Factor 4 (PF4). Clotting factors are activated. Induced hypercoagulable state. Thrombosis. Thrombocytopenia.

C: DVTs. Skin changes.

Ix: HIT antibodies.

Tx: Stop heparin. Use alternative anticoagulant. Patients are at an increased risk of clotting events.

https://www.ahajournals.org/doi/full/10.1161/circulationaha.106.632653

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Disseminated Intravascular Coagulation (DIC)

A

E:

A: Widespread clotting activation.

C: Bleeding, Sepsis, Trauma, Obstetric (HELLP, fluid embolism, haemolysis)

Ix: Thrombocytopenia. Increased bleeding time. Increased PT/PTT. Increased D-Dimer. Reduced fibrinogen (clotting factor). ​Schisiocytes on smear (microangiopathic haemolytic anaemia). Microthrombi.

↓ platelets

↓ fibrinogen

↑ PT & APTT

↑ fibrinogen degradation products

Tx: Supportive, blood components and treatment of underlying disorder.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Causes of Microcytic Anaemia

A

Causes (TAILS)

T – Thalassaemia*

A – Anaemia of chronic disease

I – Iron deficiency anaemia

L – Lead poisoning

S – Sideroblastic anaemia (congenital)

A question sometimes seen in exams gives a history of a normal haemoglobin level associated with a microcytosis. In patients not at risk of thalassaemia, this should raise the possibility of polycythaemia rubra vera which may cause an iron-deficiency secondary to bleeding.

New onset microcytic anaemia in elderly patients should be urgently investigated to exclude underlying malignancy.

*in beta-thalassaemia minor the microcytosis is often disproportionate to the anaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Causes of Normocytic Anaemia

A

Causes of normocytic anaemia (3As & 2Hs)

A – Acute blood loss

A – Anaemia of Chronic Disease (also microcytic)

A – Aplastic Anaemia

H – Haemolytic Anaemia

H – Hypothyroidism

Chronic kidney disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Causes of Macrocytic Anaemia

A

Impaired DNA synthesis - abnormally large cell

Megaloblastic

vitamin B12 deficiency

folate deficiency

Normoblastic

Alcohol

Liver disease

Hypothyroidism

Pregnancy

Reticulocytosis (haemolytic anaemia or blood loss)

Myelodysplasia

Drugs: cytotoxics (Azathioprine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Iron Deficiency Anaemia

A

E: Most common form of anaemia.

A: Reduced dietary intake (infants, vegetarian). Reduced absorption (coeliac, IBD, gastrectomy). Increased demand (pregnancy, childhood). Blood loss (gastric/colon cancer, peptic/duodenal ulcer, HMB, H.pylori).

C: Fatigue. SOB. Palpitations. Pica (abnormal dietary cravings). Hair loss.

Signs:

Pale skin

Brittle hair and nails

Conjunctival pallor

Tachycardia

Raised respiratory rate

Koilonychia (spoon-shaped nails)

Angular chelitis (mouth fissures)

Atrophic glossitis (smooth tongue)

Ix: FBC, Blood film. Microcytic MCV. Low ferritin (less stored). High Transferrin (TIBC - unbound transferrin). Hypochromic (pale). Poikilocytosis. Anisocytosis.

Tx:

  • OGD & Colonoscopy to investigate for a GI cause of unexplained iron deficiency anaemia. This is done on an urgent cancer referral for suspected gastrointestinal cancer.
  • BM biopsy may be required if the cause is unclear.

1st Line: Ferrous Sulfate 200 mg

2nd Line: Ferrous gluconate 300mg

Recheck Hb response after 2-4 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

IDA Urgent Referral Criteria

A

Urgently refer people with iron deficiency anaemia using a suspected cancer pathway for an appointment within 2 weeks if they are:

Aged 60 years or over.

Consider an urgent referral for people with iron deficiency anaemia using a suspected cancer pathway for an appointment within 2 weeks if they are:

Aged under 50 years AND present with rectal bleeding.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Plummer Vinson Syndrome

A

Associated with IDA. Triad of:

Oesophageal Webs

IDA

Dysphagia/Glossitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Sideroblastic Anaemia

A

Epidemiology

Rare. Congenital (x-linked) mainly affecting males. Acquired: Alcohol abuse, Lead poisoning, Vitamin B6 deficiency. TB therapy (Isoniazid).

Aetiology

ALAS2 mutation. Abnormal haem production - impaired incorporation of iron to form haem. Immature and dysfunctional RBCs.

Clinical Features

General features of anaemia; similar features to haemochromatosis due to iron deposition (fatigue, heart disease, liver damage, enlarged spleen, renal failure and diarrhoea).

Investigations

BM biopsy - presence of ring sideroblasts.

FBC usually shows a moderate degree of anaemia.

Pappenheimer bodies and basophilic stippling on blood film.

MCV is normal or increased, but can be low.

High serum iron and ferritin. Low TIBC.

The blood film shows a dimorphic population of both normal and hypochromic red blood cells.

Management

Treatment is mainly supportive

Red cell transfusion is given for symptomatic anaemia

Iron chelation with desferrioxamine should be considered after 20-25 units of red cells have been received.

Avoid alcohol and reduce vitamin C intake, as these increase iron absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Anaemia of Chronic Disease

A

Epidemiology

Chronic inflammatory disease states such as COPD, DM, Autoimmune disorders, infections and malignancy.

Second most common anaemia.

Aetiology

Continuous inflammation by Chronic disease state results in impaired iron metabolism and hence RBC production and lifespan.

Clinical Features

General clinical features of anaemia of Fatigue, Pallor and SOB.

Investigations

Normocytic anaemia. Low iron. Normal-low transferrin (TIBC). Low transferrin saturation. Normal/increased ferritin.

Treatment

Treat underlying cause

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Lead Poisoning

A

Epidemiology

Classically presents in painters/children playing with old paint.

Aetiology

Defective ferrochelatase and ALA dehydratase function

Clinical features

Abdominal pain

Peripheral neuropathy (mainly motor)

Fatigue

Constipation

Blue lines on gum margin (only 20% of adult patients, very rare in children)

Investigations

Blood Lead Level (> 10 mcg/dl is significant)

FBC: microcytic anaemia.

Blood film: red cell abnormalities including basophilic stippling and clover-leaf morphology

raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria

urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased)

Treatment

Dimercaptosuccinic acid (DMSA)

D-penicillamine

EDTA

Dimercaprol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Vitamin B12 Deficiency

A

Epidemiology & Aetiology

Impaired absorption - pernicious anaemia (autoimmune destruction of intrinsic factor/parietal cells). Crohn’s Disease (damage to enterocytes in terminal ileum). Gastric bypass. Fish tapeworm. Bacterial overgrowth.

Reduced dietary intake (vegans)

Clinical Features

Glossitis - painful large red tongue

Neurological: Poor reflexes, peripheral neuropathy (demyelination) with symmetrical parasthesia affecting legs > arms.

Subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia

Neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy

SOB

Fatigue

IHD

Investigations

FBC: Macrocytic megaloblastic anaemia. Pancytopenia (Low RBC, WBC and Platelets).

Blood Smear: Hypersegmented neutrophils.

Anti-intrinsic factor antibodies (pernicious anaemia)

Management

Pernicious Anaemia: IM hydroxocobalamin (B12)

Neurological involvement: IM hydroxocobalamin (B12)

Dietary: Initially IM hydroxocobalamin (B12) for 2 weeks then oral cyanocobalamin tablets 50–150 micrograms daily

https://cks.nice.org.uk/topics/anaemia-b12-folate-deficiency/management/management/

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Folate Deficiency

A

Epidemiology

Associated with Neural Tube Defects (NTDs) - anencephaly or spina bifida.

Aetiology

Increased demand (pregnancy)

Reduced dietary intake (> 6 weeks)

Reduced absorption (excessive alcohol, drugs - phenytoin, trimethoprim, sulfasalazine and methotrexate)

Clinical Features

Glossitis - painful large red tongue

Neurologic: Poor reflexes, peripheral neuropathy (demyelination), memory problems.

SOB

Fatigue

IHD (increased homocysteine)

Investigations

FBC: Macrocytic megaloblastic anaemia. Pancytopenia (Low RBC, WBC and Platelets).

Blood Smear: Hypersegmented neutrophils.

Anti-intrinsic factor antibodies (pernicious anaemia)

Management

Pregnancy: folate supplementation: 400 micrograms (μg) daily before pregnancy and throughout the first 12 weeks. 5 milligrams of folic acid a day for women who are planning a pregnancy, or are in the early stages of pregnancy, if:

  • they (or their partner) have a NTD
  • have had a previous baby with a NTD
  • (or their partner) have a family history of NTD
  • have diabetes.
  • have epilepsy.

Absorbtion: Stop offending medications

Dietary: Prescribe oral folic acid 5 mg daily for 4 months

https://cks.nice.org.uk/topics/anaemia-b12-folate-deficiency/management/management/

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Fanconi Anaemia

A

Epidemiology

Autosomal recessive

Aetiology

Clinical features

Haematological: aplastic anaemia (with pancytopenia), increased risk of AML

Neurological: developmental delay

‘Bird-like’ facies

Skeletal abnormalities: short stature, thumb/radius abnormalities

Cafe au lait spots

Investigations

Treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Aplastic Anaemia

A

Epidemiology

Peak incidence ~30 years of age

Aetiology

Generally idiopathic. Definable causes: radiation & toxins. Congenital: Fanconi anaemia, dyskeratosis.

Drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold

Toxins: benzene

Infections: parvovirus, hepatitis

Commonest form is autoimmune destruction of Haematopoetic Stem Cells (HSCs).

Clinical Features

Fatigue

Pallor

Mucosal Bleeding

Petichiae

Recurrent infections

Investigations

FBC: Anaemia & Pancytopenia (Low RBC, WBC, Platelets)

Increased EPO

Reduced reticulocyte count

Definitive Diagnosis: BM Biopsy with low HSCs, normal cellular morphology in absence of infiltrative disorder

Treatment

Dependent on age

Allogenic stem cell transplant

Immunosuppressants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Haemolytic Anaemias

A

E:

A:

C:

Ix:

Tx:

28
Q

Autoimmune Haemolytic Anaemia

A

E:

A:

C:

Ix:

Tx:

29
Q

Thalassemia

A

E: Autosomal recessive. Major (symptomatic) and Minor (asymptomatic/mild anaemia).

A: Defect in either alpha or beta globin chains.

C: Splenomegaly. Chipmunk facies (pronounced forehead and cheekbones) - Major. RBCs in other locations. Poor growth and development (failure to thrive).

Ix:

FBC shows a microcytic anaemia

Haemoglobin electrophoresis is used to diagnose globin abnormalities

DNA testing can be used to look for the genetic abnormality

Tx:

Iron chelation (remove excess iron)

Splenectomy

BM transplant can potentially be curative

30
Q

Alpha-thalassaemia

A

E: Autosomal recessive. CIS (same; Asians) or Trans (different; Africans) deletions.

A: Defects in alpha-globin chains. Chromosome 16. Disease severity is dependent on number of genes involved.

  • 1 or 2 alpha globulin alleles; hypochromic and microcytic, but the Hb level would be typically normal. MILD anaemia.
  • 3 alpha globulin alleles; hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease. SEVERE anaemia.
  • 4 alpha globulin alleles (i.e. homozygote) then death in utero (Bart’s Hydrops fetalis).

Ix: FBC, Haemoglobin electrophoresis & DNA testing. Microcytic hypochromic anaemia. Target cells on blood smear. Fetal DNA (CVS or Amniocentesis).

Tx:

Monitoring FBC

Monitoring for complications

Blood transfusions

Splenectomy may be performed

BM transplant can be curative

31
Q

B-Thalassemia Major

A

E: Mediterranean, African and South-East Asians.

A: Homozygous for deletion genes. Free alpha chains form inclusions in RBCs - leads to haemolysis of RBCs. Ultimately causes increased RBC production.

C: Splenomegaly. Failure to thrive in early childhood (first 3-6 months of life). Severe microcytic anaemia. Chipmunk facies (excess RBC production). Jaundice (byproduct of RBC breakdown). Secondary Haemochromatosis (excess iron).

Ix: FBC, Haemoglobin electrophoresis (low HbA, high HbF and HbA2) & DNA testing. Microcytic hypochromic anaemia. High Iron, ferritin and transferrin (TIBC). Target Cells present on blood smear.

Tx:

Iron chelation (remove excess iron); deferoxamine

Splenectomy

BM transplant can potentially be curative

32
Q

B-Thalassemia Minor

A

E: Mediterranean, African and South-East Asians.

A: Heterozygous for gene deletion - one normal and one non-functioning gene.

C: Mild microcytic anaemia

Ix: FBC, Haemoglobin electrophoresis & DNA testing.

Tx:

Monitoring

No active treatment

33
Q

B Thalassemia intermedia

A

E: Mediterranean, African and South-East Asians.

A:Homozygousfordefective gene - two defective genes or one defective and one deletion (non-functioning) gene.

C: Significant microcytic anaemia

Ix: FBC, Haemoglobin electrophoresis & DNA testing.

Tx:

Monitoring

Occassional blood transfusions

Iron chelation (if increased transfusions)

34
Q

Sickle-Cell Anaemia

A

Epidemiology

Autosomal recessive. More prevalent in Africans. Selective advantage for malaria (reduced severity).

Aetiology

Sickle-cell shaped RBCs (beta-globin) due to deoxygenation. Prone to destruction, thus haemolytic anaemia. Haemoglobin S variant (HbS). Abnormal gene for beta-globin on chromosome 11.

Two forms:

Sickle Cell Trait: only one copy of the gene (heterozygous). Asymptomatic.

Sickle Cell Disease: two copies of the gene (homozygous). Symptomatic.

Clinical features (4-6m after birth)

Expansion of skull medullary cavities: elarged cheeks, ‘hair on end’ appearance of skull.

Extramedullary Haematopoesis: Hepatomegaly

Vaso-occlusion (multi-organ): Dactylitis (infancy), Pain crisis, AVN, Splenic infarct/sequestration, Recurrent infections, Stroke/Moya-Moya, Acute chest syndrome, Priaprism.

Investigations

Pregnant women at risk are offered testing.

Newborn heel prick test at 5d.

Normocytic anaemia. Raised reticulocyte count (compensatory).

Definitive Diagnosis:Haemoglobin Electrophoresis.

Management

Avoid dehydration and other triggers of crises

Ensure vaccines are up to date

Antibiotic prophylaxis to protect against infection with Penicillin V (phenoxymethypenicillin)

Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.

Blood transfusion for severe anaemia

BM transplant can be curative

35
Q

Sickle Cell Crisis

A

Epidemiology

Sickle cell crisis is an umbrella term for a spectrum of acute crises related to the condition. These range from mild to life threatening.

Aetiology

They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.

Clinical Features

Vaso-occlusive Crisis (AKA painful crisis)

Distal ischaemia. Associated with dehydration and raised haematocrit. Symptoms are typically pain, fever and those of the triggering infection. It can cause priapism in men by trapping blood in the penis causing a painful and persistent erection. This is a urological emergency and is treated with aspiration of blood from the penis.

Splenic Sequestration Crisis

Splenic sequestration crisis is caused by RBCs blocking blood flow within the spleen. This causes an acutely enlarged and painful spleen. The pooling of blood in the spleen can lead to a severe anaemia and circulatory collapse (hypovolaemic shock).

Splenic sequestration crisis is considered an emergency. Management is supportive with blood transfusions and fluid resuscitation to treat anaemia and shock.

Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises. Recurrent crises can lead to splenic infarction and therefore susceptibility to infections.

Aplastic Crisis

Aplastic crisis describes a situation where there is a temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19 (fith disease aka ‘slapped cheek’).

It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.

Investigations

Crisis Management

Analgesia e.g. opiates

Rehydrate

Oxygen

Consider antibiotics if evidence of infection

Blood transfusion

Exchange transfusion: e.g. if neurological complications

NSAIDs such as ibuprofen should be avoided where there is renal impairment.

Longer-term management

Hydroxyurea increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes

NICE CKS suggest that sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years

36
Q

Pernicious Anaemia

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

37
Q

Acute Myeloid Leukaemia (AML)

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

38
Q

Acute Lymphocytic Leukaemia (ALL)

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

39
Q

Chronic Myeloid Leukaemia (CML)

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

40
Q

Chronic Lymphocytic Leukaemia (CLL)

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

41
Q

Hodgkin’s Lymphoma

A

Epidemiology

Bimodal age distribution - 20 and 75 years.

Aetiology

Proliferation of lymphocytes. Nodular sclerosing (70%)

Clinical features

Lymphadenopathy - asymmetrical non-tender and rubbery lymph nodes (pain with alcohol)

Fever (>38)

Weight loss (>10% in last 6m)

Night sweats

Investigations

Lactate dehydrogenase may be raised (non-specific)

Normocytic anaemia, eosinophilia

Definitive - Lymph node biopsy reveals presence of Reed Sternberg Cells (abnormally large B-Cells, multinucleated, ‘owl’)

Treatment

Chemotherapy (risk of leukaemia and infertility)

Radiotherapy (risk of cancer, hypothyroidism)

42
Q

Non-Hodgkin’s Lymphoma

A

Epidemiology

Elderly with one-third of cases occurring in those over 75 years of age. RFs include immunosuppression (HIV), Viruses (EBV, Hep B/C), radiation or pesticide exposure (trichloroethylene).

Aetiology

Proliferation of B-Cell (70%) lymphocytes. Various types:

Burkitt lymphoma (B-cell) is associated with EBV, malaria and HIV. Young males.

MALT lymphoma affects the mucosa-associated lymphoid tissue, usually around the stomach. It is associated with H. pylori infection.

Diffuse large B cell lymphoma (B-cell) often presents as a rapidly growing painless mass in patients over 65 years.

Clinical features

Lymphadenopathy - asymmetrical non-tender and rubbery lymph nodes (cervical, axillary and inguinal)

Fever (>38)

Weight loss (>10% in 6m)

Night sweats

Extranodal disease (differentiating feature from Hodgkin’s): Gastric (dyspepsia, dysphagia, weight loss, abdominal pain), BM (pancytopenia, bone pain), lungs, skin, CNS (nerve palsies)

Compression syndromes: SVC Syndrome, Spinal Cord compression

BM infiltration: Anaemia, neutropenia or thrombocytopenia

Investigations

Lactate dehydrogenase may be raised (non-specific)

Definitive - Lymph node biopsy reveals presence of lymphocytic cells with ‘starry sky’ appearance

CT, MRI & PET for staging.

Treatment

Watchful waiting

Chemotherapy (risk of leukaemia and infertility)

Monoclonal antibodies such as rituximab

Radiotherapy (risk of cancer, hypothyroidism)

Stem cell transplantation

43
Q

Burkitt’s Lymphoma

A

Epidemiology

Young males. Associated with EBV, Malaria and HIV.

Aetiology

Aggressive form of B-Cell lymphoma. C-myc gene translocation, usually t(8:14).

2 Forms

Endemic (African): involves maxilla or mandible (rapid focal tooth loosening)

Sporadic (American): GIT, pre/para-aortic lymph nodes

Clinical features

Extra-nodal involvement:

Investigations

Definitive: Lymph node biopsy reveals B-lymphocyte cells with ‘starry sky’ appearance.

Treatment

Chemotherapy; tendency to induce Tumour Lysis Syndrome:

hyperkalaemia

hyperphosphataemia

hypocalcaemia

hyperuricaemia

acute renal failure

Rasburicase is given alongside chemo to prevent this. Treatment of TLS involves

44
Q

Staging of Lymphomas (Ann Arbor)

A

Stage 1: Confined to one region of lymph nodes.

Stage 2: In more than one region but on the same side of the diaphragm (either above or below).

Stage 3: Affects lymph nodes both above and below the diaphragm.

Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.

45
Q

Myeloma (multiple)

A

Epidemiology

>60 years with unexplained bony pain (lower back/thoracic). Second most common haematological malignancy.

Aetiology

Plasma (B lymphocyte) cells

Clinical features (CRAB)

C – Calcium (elevated due to inreased osteoclastic activity). Confusion, muscle weakness, constipation, thirst, and polyuria (due to hypercalcaemia).

R – Renal failure (immunoglobin deposition)

A – Anaemia (normocytic, normochromic) from replacement of bone marrow.

B – Bone lesions/pain (lytic lesions on X-ray; ‘raindrop’ skull). Lower back. Sensory loss, paraesthesia, limb weakness, walking difficulty, and sphincter disturbance (due to spinal cord compression).

Investigations (BLIP)

BBence–Jones protein (request urine electrophoresis)

L – Serum‑free Light‑chain assay

I – Serum _Immunoglobulins (_IgA/IgG proteins)

P – Serum Protein electrophoresis

Pancytopenia: Anaemia (‘crowding-out’ BM) and Thrombocytopenia (FBC); Raised urea and creatinine (U&E) and Raised calcium. Raised ESR.

Raised Plasma Viscosity (PV): easily bruise/bleed.

Imaging: X-rays of symptomatic areas (to rule out pathological fractures)

Blood film: rouleaux formation

Definitive diagnosis: BM Biopsy (aspiration and trephine)

Treatment

First line treatment usually involves a combination of chemotherapy with:

Bortezomid

Thalidomide

Dexamethasone

Autologous Stem Cell transplant - younger patients

VTE prophylaxis (LMWH or aspirin)

Myeloma bone disease can be improved using bisphosphonates (zoledronic acid). These suppress osteoclast activity.

Radiotherapy to bone lesions can improve bone pain.

Orthopaedic surgery can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures.

Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain

46
Q

Primary Myelofibrosis

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

47
Q

Polycythemia Ruba Vera (PRV)

A

E:

A:

C:

Ix:

Tx:

48
Q

Essential Thrombocythaemia

A

E:

A:

C:

Ix:

Tx:

49
Q

Myelodysplastic Syndrome

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

50
Q

Von Willebrand Disease (VWD)

A

Epidemiology

Commonest inherited cause of haemophilia (abnormal bleeding). Autosomal dominant.

Aetiology

Deficiency, absence or malfunctioning of a glycoprotein called Von Willebrand Factor (VWF). Family history is relevant.

Clinical features

Patients present with a history of unusually easy, prolonged or heavy bleeding:

Bleeding gums with brushing

Epistaxis

HMB (menorrhagia)

Heavy bleeding during surgical operations

Investigations

Clinical diagnosis is made on history of abnormal bleeding, family history, bleeding assessment tools and laboratory investigations.

Prolonged _APTT (_intrinsic pathway) and bleeding time. Normal _PT(_extrinsic pathway). Low VWF.

Management

Managed in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding):

Desmopressin can be used to stimulate the release of VWF

VWF infusion

Factor VIII is often infused along with plasma-derived VWF

51
Q

Factor V Leiden

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

52
Q

Haemophillia

A

Epidemiology

X-linked recessive. Males (50% chance of affected if maternal carrier). Females (100% carriers if paternal carrier or 25% carriers if maternal carrier).

Aetiology

Severe bleeding disorder. Three forms:

Haemophilia A: Factor VIII deficiency

Haemophilia B: Factor IX deficiency

Haemophilia C*: Factor XI deficiency (ashkenazi jews)

*Autosomal recessive so can affect males and females.

Clinical features

Most cases present in neonates or early childhood. It can present with intracranial haemorrhage, haematomas and cord bleeding in neonates.

Classically presents with spontaneous bleeding into joints (haemoathrosis) and muscles. If untreated this can lead to joint damage and deformity.

Investigations

Bleeding scores, coagulation factor assays and genetic testing.

PROLONGED APTT (intrinsic pathway)

NORMAL bleeding time, thrombin time, prothrombin time (PT) - extrinsic pathway

Treatment

Acute episodes of bleeding or prevention of excessive bleeding during surgical procedures involve:

Infusions of the affected factor (VIII or IX) for major bleed (antibodies against these can develop rendering these treatments ineffective). OR

Cryoprecipitate/FFP if infusions are unavailable

Desmopressin to stimulate the release of von Willebrand Factor (minor bleed)

Antifibrinolytics such as tranexamic acid

AVOID NSAIDS AND IM INJECTIONS

53
Q

Platelet vs. Coagulation disorders

A

Platelet Disorders (Primary)

Affects mucous membranes (gingival, GI, vaginal)

Petechiae (multiple)

Prolonged bleeding from cuts

Family history rare

Prolonged Bleeding Time

Examples include thrombocytopenias i.e. VWD, ITP

Coagulation Disorders (Secondary)

Affects joint spaces (haemarthrosis)

Ecchymoses (large bruising)

Haematomas (muscles)

Delayed-onset bleeding

Family history common

Prolonged APTT (Intrinsic pathway) & PT (extrinsic pathway). Normal bleeding time

Examples include Haemophilia A/B, Factor V Leiden, LD, DIC, Vitamin K deficiency

54
Q

DVT & Thromboembolism

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

55
Q

Anticoagulation duration following provoked DVT

A

3 months (active cancer 3-6m)

56
Q

Anticoagulation duration following unprovoked DVT

A

6 months

57
Q

Causes of unprovoked DVT

A

X

58
Q

Causes of provoked DVT

A

X

59
Q

Chronic Fatigue Syndrome

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

60
Q

Haemochromatosis

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

61
Q

Hyperlipidaemia

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

62
Q

Hyposplenism

A

Epidemiology

Aetiology

Splenectomy

Sickle-cell

Coeliac disease, Dermatitis herpetiformis

Graves’ disease

Systemic lupus erythematosus

Amyloid

Clinical features

Investigations

Blood smear: Howell-Jolly bodies. Siderocytes

Management

63
Q

Pancytopenia

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

64
Q

Wilson’s Disease

A

E:

A:

C:

Ix:

Tx:

65
Q

Porphyrias

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

66
Q

Glucose-6-Phosphate Deficiency (G6PD)

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment

67
Q

Antiphospholipid Syndrome

A

Epidemiology

Aetiology

Clinical features

Investigations

Treatment