Haem - symptoms + signs

Question 1

Sickle cell anaemia symptoms + signs

Answer 1

Dactylitis
Acute Chest syndrome
Haemolytic anaemia
Priapirsm
Aplastic crisis

Question 2

Signs of haemolysis

Answer 2

Hb low
Haptoglobin low (problem of intravascular haemolysis)
Unconjugated bilirubin raised
LDH raised
High urobilinogen

Question 3

Haemolytic uraemic syndorme triad

Answer 3

MAHA (microangiopathic haemolytic anaemia)
Thrombocytopenia
AKI

Question 4

Thrombotic Thrombocytopaenic purpura pentad

Answer 4

MAHA
Decreased platelets
AKI
Temperature
Swinging CNS signs
Antiglobulin negative

Question 5

HUS symptoms

Answer 5

Classic triad
• Microangiopathic haemolytic anaemia
• Thrombocytopenia
• AKI

• Most adults remain asymptomatic

Children
GI features
• Profuse diarrhoea that turns bloody 1-3 days later in children
• Fever, abdominal pain, vomiting

Renal features
• Oliguria
• Creatinine

Haemolytic features
• Jaundice
• Scleral icterus
• Conjunctival pallor

Question 6

In broad terms, what is myelofibrosis?And 3 features

Answer 6

proliferation of an abnormal clone of haematopoietic stem cells in the BM + other sites results in fibrosis or the replacement of the marrow with scar tissue

Abnormal production of RBC, WBC, Plt
Marrow fibrosis
Extramedullary haematopoiesis

Question 7

Myelofibrosis symptoms + signs

Answer 7

Clinical hallmarks
• Leukoerythroblastosis
• Splenomegaly - results in early satiety, generalised abdominal discomfort, LUQ discomfort

•	Constitutional symptoms – hypercatabolic state as a result of high cell turnover 
o	Weight loss (>10% over 6 months)
o	Night sweats
o	Low-grade fever
o	Cachexia
o	Fatigue
o	Pruritus

• Hepatomegaly present in about 50% of patients – due to multi-organ extra-medullary haematopoiesis
• Pallor
• Petechiae and ecchymosis
• Neutropenia may cause opportunistic infection e.g. oral thrush
• Lymphadenopathy
• Portal HTN
• Gout

Due to extra-medullary haematopoiesis
 •	Pulmonary HTN
•	Spinal cord compression
•	Focal seizures
•	Ascites
•	Haematuria
•	Haemoptysis
•	Pericardial/pleural effusion
•	Respiratory failure

Question 8

TTP symptoms

Answer 8

• MAHA
• Thrombocytopenia
  o Epistaxis, bruising, petechiae, purpura, gingival bleeding, haematuria, menorrhagia, GIB, retinal haemorrhage, haemoptysis
• AKI
  o Proteinuria, micro-haematuria, raised U + Cr
• Neurological dysfunctions
  o Confusion, headache, focal abnormalities (paresis, aphasia, dysarthria, visual problems), seizures, encephalopathy, coma
• Fever

• Digestive symptoms
o N, V, D, abdo pain
o Can be secondary to microthrombi in the bowel

• Chest pain, HF, arrythmias hypotension
• Jaundice – 2y to haemolysis
• Severe HTN
• Splenomegaly

Question 9

Hodgkin’s lymphoma symptoms

Answer 9

• Non tender, firm rubbery lymphadenopathy (most commonly involving the cervical/supraclavicular node chain)
• Mediastinal lymphadenopathy (often asymptomatic but can cause dyspnoea, cough, chest pain, SVC syndrome)
• Pain at sites of lymphadenopathy after drinking alcohol

• B symptoms
o Weight loss >10% over 6 months
o Fever >38
o Night sweats

• Hepatomegaly, splenomegaly in advanced disease(SVC syndrome – dyspnoea, cough, orthopnoea, facial + upper extremity oedema, dilated neck veins)

Question 10

Malaria symptoms

Answer 10

• Fever - Characteristic paroxysms of severe cold / rigors followed by severing sweating - cyclical fevers
• Chills
• Sweats
• Headache
• Arthralgia
• Myalgia
• Weakness
• Anorexia
• Diarrhoea

Question 11

Malaria signs

Answer 11

• Splenomegaly
• Hepatomegaly
• Jaundice
• +/- abdominal tenderness

Question 12

Malaria - severe disease symptoms + signs

Answer 12

Signs of severe disease (P. falciparium)
•	Impaired consciousness
•	SOB
•	Bleeding
•	Hypovolaemia
•	Hypoglycaemia
•	Fits
•	AKI
•	Nephrotic syndrome
•	ARDS (during treatment)

Question 13

Myelodysplasia signs + symptoms

Answer 13

• Asymptomatic – typically patients are asymptomatic + the disease is identified based on laboratory findings
• Anaemia – fatigue, exercise intolerance, pallor, cardiac failure, tachycardia
• Leukopenia
o If granulocyte depletion occurs - recurrent/unusual infections or overwhelming sepsis
• Thrombocytopenia – petechiae, purpura, bruising, nosebleeds, bleeding from gums after brushing teeth, ecchymoses

Question 14

Hallmark of haemophilia

Answer 14

Musculoskeletal bleeding (intramuscular haematoma, haemarthroses)
Increased pressure can lead to compartment syndrome or nerve palsies

Question 15

Type of bleeding more common in haemophilia B than A

Answer 15

GI + mucosal haemorrhage - haematemesis, melaena, frank red blood per rectum, abdominal pain

Question 16

Signs of heamartoma

Answer 16

Warmth
Pain
Stiffness
Refusal to use a joint due to muscle haematoma or hemarthrosis

Question 17

Haemochromatosis signs + symptoms

Answer 17

• Fatigue
• Weakness
• Lethargy

• Arthropathy –> Arthralgias
o Calcium pyrophosphate crystal deposition
o Pseudogout
o Chronic arthropathy

• Diabetes
• Hypogonadism (impotence, loss of libido, amenorrhoea)

• Heart disease

• Skin pigmentation
o May begin as bronzing of the skin but then progress to grey or brown with slate-grey patches in the mouth

• Neurological or psychiatric symptoms – impaired memory, mood swings, irritability, depression

Liver
•	Hepatomegaly
•	Fibrosis
•	Cirrhosis
•	Hepatocellular cancer

Question 18

Leukaemia general symptoms and signs

Answer 18

• Anaemia
• Fatigue, dizziness lethargy, pallor, breathlessness, tachycardia
• Neutropenia
• Fever + other features of infection (e.g. pneumonia)
• Thrombocytopenia
• Bruising, petechiae, bleeding
• Lymphadenopathy
• Leucocytosis (blood becomes very viscous - visual disturbance, priapism, CVA, confusion)
• Bone pain (if acute leukaemia)
• Hepatosplenomegaly

Hyperuricaemia due to rapid cell turnover causes

• Gout (acute)
• Renal failure (chronic)

Question 19

Evidence of cell infiltration in ALL

Answer 19

o Hepatosplenomegaly
o Bone pain
o Testicular enlargement (painless, unilateral)
o Thymic enlargement (mediastinal compression -stridor, wheeze, SVCO)
o Gum hypertrophy
o Renal enlargement
o CN palsies (esp. 3, 4, 6, 7)
o CNS (papilloedema, nuchal rigidity, meningisums, headache, irritability, altered mental status)

Question 20

What are sanctuary sites?

Answer 20

Sites where systemic chemo can’t reach the cells

Testes + CNS

Question 21

Multiple myeloma symptoms + signs

Answer 21

• Lethargy due to anaemia
• Hypercalcaemia (thirst, constipation, nausea, confusion)
• Bone pain (particularly backache)
• Pathological fractures
• Renal impairment
• Spinal cord/nerve root compression
• Anorexia
• Dehydration (due to proximal tubule dysfunction from L-chain precipitation)
• Recurrent bacterial infection
• Bleeding and/or bruising
• Amyloidosis (cardiac failure, nephrotic syndrome)
• Dizziness, confusion, blurred vision, headaches, epistaxis, CVA (due to hyperviscosity)
• skeletal lesions (osteolytic lesions, pepperpot skull, pathological fractures)

Question 22

Sickle cell disorder symptoms + signs

Answer 22

Symptoms + signs begin bn 3-6m when HbF levels are falling
• Anaemia (haemolysis)
• Scleral icterus, jaundice, bilirubin gallstones (excess unconjugated bilirubin due to haemolysis)
• Increased reticulocytes- Intramedullary haematopoiesis
• Enlarged cheeks
• Hair on end appearance on skull XR- Extra-medullary haematopoiesis
• Hepatomegaly

• Vaso-occlusive/Sickle cell crises
• Splenic sequestration
• Aplastic crisis
• Hyper haemolytic crisis

Question 23

Describe the vasoocclusive crisis/sickle cell crisis

Answer 23

Precipitated by cold, infection, dehydration, exertion, ischaemia
• Pain (from oxygen deprivation of tissues + avascular necrosis of the BM)
• Dactylitis
• Avascular necrosis of the femur
• Priapism

• Cerebral vasculature - Stroke, mental status changes, moyamoya (haemorrhage from microaneurysms which develop around infarctions to bypass blocked arteries)
• Kidneys - Haematuria, proteinuria, loin pain (renal papillary necrosis)

• Lungs - acute chest syndrome
o =New pulmonary infiltrate on the CXR combined with >1: fever, cough, sputum production, tachypnoea, dyspnoea, new-onset hypoxia
o Chest pain, SOB, cough
o Lung infections tend to predominate in children, infarcts predominate in adults
o Pt isn’t breathing efficiently - oxygen levels will sink even lower - this will precipitate more sickling

• Spleen - splenic infarct
• Abdomen - acute abdominal distension, pain (mesenteric sickling and bowel ischaemia)
• Eyes - hyphaema, retinal occlusion

Question 24

Describe the aplastic crisis in sickle cell disease

Answer 24

Temporary cessation of erythropoiesis, causing severe anaemia
• Precipitated by infection with parvovirus B19
• Drop in Hb over one week
• Recovery may be spontaneous but transfusion is usually required
• With the severe anaemia associated with an aplastic crisis, patients may present with high-output CHF

Question 25

Describe splenic sequestration in sickle cell disease

Answer 25

* Splenomegaly * Acute splenic sequestration – acute fall in Hb, markedly elevated reticulocyte count, acute increase in spleen size * Life-threatening complication * Instead of just occluding the blood vessels, RBC can also get trapped inside the spleen along with a large portion of the circulating blood volume - this causes the spleen to massively enlarge * Rapid drop in haemoglobin - circulatory collapse - hypovolaemic shock * Recurrent splenic sequestration is an indication for splenectomy * Not having a functional spleen - pt susceptible to encapsulated bacteria (Strept. Pneumoniae, Haemophilus influenza, N. Meningitis, Salmonella species)

Question 26

Describe the hyperhaemolytic crisis in sickle cell disease

Answer 26

Hyper haemolytic crisis • Excessive haemolysis • Uncommon • During painful crises here may be a marked increase in the rate of haemolysis + drop in Hb

Question 27

A thalassaemia Signs and symptoms of - Silent carrier (3 α genes working) - A thalassaemia trait (2 α genes working) - A thalassaemia intermedia/ HbH (1 α gene working) - A thalassaemia major /Hb Bart's(0 α genes working)

Answer 27

Thalassaemia A - symptoms of haemolytic anaemia (e.g. pallor, hepatosplenomegaly) at birth Silent carrier - anaemic, low MCV, low MCH, asymptomatic A thalassaemia trait - anaemic, low MCV, low MCH, asymptomatic A thalassaemia intermedia/ HbH- anaemic, low MCV, low MCH, splenomegaly, jaundice, bone changes A thalassaemia major/ Hb Bart's - severe non-immune intrauterine haemolytic anaemia, foetuses develops hydrops fetalis, usually fatal

Question 28

``` B thalassaemia Signs and symptoms of β thalassaemia trait (-/β2) β thalassaemia intermedia (β+/β0 or β+/β+) β thalassaemia major (βο/βο) ``` o Normal beta globin chain synthesis - β2 o Reduced beta globin chain synthesis - β+ o Absent beta globin chain synthesis - β0

Answer 28

Thalassaemia B - symptoms of haemolytic anaemia (e.g. pallor, hepatosplenomegaly) several months after birth o β thalassaemia trait - anaemic, low MCV, low MCH, asymptomatic o β thalassaemia intermedia – anaemia, low MCV, low MCH, splenomegaly, bone changes, high HbF o β thalassaemia major– very low MCV, very low MCH, severe haemolytic anaemia, hepatosplenomegaly, chronic transfusion dependency high HbF

Question 29

Symptoms + signs of thalassaemia

Answer 29

Thalassaemia A - symptoms of haemolytic anaemia (e.g. pallor, hepatosplenomegaly) at birth Thalassaemia B - symptoms of haemolytic anaemia (e.g. pallor, hepatosplenomegaly) several months after birth • Β thalassaemia major in infancy - failure to thrive, vomiting, sleepiness, stunted growth, irritability • Ineffective erythropoiesis creates a hypermetabolic state with fever • Marked pallor, dizziness, SOB, fatigue • Exercise intolerance, cardiac flow murmur, HF secondary to severe anaemia • Bone deformities due to extramedullary haematopoiesis o Chipmunk facies – frontal bossing, prominent facial bones, dental malocclusion • Hepatosplenomegaly • Jaundice, gallstones (due to haemolysis) • Secondary haemochromatosis (due to haemolysis) • Iron overload can cause endocrinopathy with diabetes, thyroid, adrenal, pituitary disorders

Question 30

VWD symptoms + signs

Answer 30

* Mucocutaneous bleeding - epistaxis, menorrhagia, post natal haemorrhage (as opposed to haemophilia where musculoskeletal injury is the hallmark of the disease) * GI + mucosal haemorrhage * Bleeding from minor wounds * Postoperative bleeding easy + excessive bleeding * FHx of bleeding

Question 31

PV symptoms + signs

Answer 31

* Starts at the plethoric stage, progresses to the spent stage * Aquagenic pruritus worse after a hot shower/bath (increased basophils + mast cells release histamine) * Splenomegaly * Pt may look plethoric + have a ruddy complexion * Non-specific complaints of lethargy + tiredness * Thrombosis (1/3) – stroke, MI, DVT, PE * Headache, dizziness, sweating (in decreasing order of frequency) * Peptic ulceration * GI haemorrhage, bleeding from gums, easy bruising * Gout + kidneys tones (build up of uric acid) * HTN

Question 32

Antiphospholipid syndrome symptoms + signs

Answer 32

Triad of - Recurrent miscarriages - Thromboembolism - Thrombocytopenia * Peripheral artery thrombosis, DVT * MI, Stroke * Miscarriage (placental infarction), pre-eclampsia, IUGR * Livedo reticularis (swelling of the venules due to clots), purpura, skin ulceration * CVD, sinus thrombosis, headaches, seizures * PE, Pulmonary HTN * Renal failure * Retinal thrombosis * Arthritis/athralgia * Catastrophic antiphospholipid syndrome  rapid organ failure due to generalised thrombosis * Thrombocytopenia, haemolytic anaemia * Mitral valve disease or aortic valve disease – usually regurgitation +/- stenosis ``` Meded symptoms + signs summary • Recurrent miscarriages (3+) • VTE (venous problems) • Stroke/MIs, HTN (arterial problems) • Livedo reticularis (mottled) ```

Question 33

Lymphadenompathy in CLL

Answer 33

Enlarged rubbery non-tender lymph nodes

Question 34

MM crab

Answer 34

``` Calcium raised (>2.6 mmol/L) Renal impairment (serum Cr >176.8 μmol/L) Anaemia (Hb <100g/L or 20g below normal range) Bone pain, osteoporosis pathological fractures, lytic bone lesions ```

Question 35

Classic triad of B12 deficiency + other symptoms

Answer 35

Paraesthesia Glossitis Tiredness ``` Weakness Fatigue Glossitis Changes in bowel habit (derangement in tissues with high cell turnover) ``` Peripheral neuropathy Optic atrophy Dementia Subacute combined degeneration of the spinal cord (pyramidal tract weakness, mixed UMN + LMN signs, lower limb weakness) ``` Patients therefore present with Paraesthesia Muscle weakness Visual impairments Psychiatric disturbance DIFFICULTY WALKING ```

Question 36

Non-hodgkin's lymphoma symptoms + signs

Answer 36

* Systemic symptoms less common than in HL * Organ involvement more common than in HL – skin rashes, headache, hepatosplenomegaly, sore throat, cough * Night sweats * Weight loss * Fever * Fatigue/malaise * Lymphadenopathy * Splenomegaly

Question 37

DIC symptoms + signs plus acute and chronic presentation of DIC

Answer 37

``` • Microvascular/macrovascular thrombosis o Purpura fulminans o Gangrene o Acral cyanosis o Delirium/coma ``` ``` • Generalised bleeding (evidenced by at least 3 unrelated sites) o Petechiae o Ecchymosis o Oozing o Haematuria ``` ``` • Circulatory collapse o Oliguria o Hypotension o Tachycardia o Confusion, disorientation ``` * Haemolytic features (jaundice, conjunctival pallor) * Signs of ARDS * Osmosis.org: widespread clotting, organ ischaemia, MAHA, decreased plt + clotting factors Acute DIC: petechiae, purpura, ecchymoses, epistaxis, mucosal bleeding, hemorrhage, respiratory distress Chronic DIC: signs of deep venous or arterial thrombosis or embolism

Question 38

Aplastic anaemia symptoms + signs

Answer 38

* Anaemia – fatigue, pallor, chest pain, SOB * Thrombocytopenia – increased risk of bleeding from minor injuries, mucosal bleeding, petechiae * Leukocytopenia – Recurrent infections, sepsis * (preceding hx of jaundice, usually 2-3 months before may indicate a post-hepatic aplastic anaemia)

Question 39

triad of haemochromatosis

Answer 39

bronze skin hepatomegaly DM