clinical haematology Flashcards
(81 cards)
1
Q
define disseminated intravascular coagulation (DIC)
A
serious illness => disorder of the clotting cascade => depleted platelets and coagulation factors
- acute overt = EMERGENCY + significant depletion => bleeding
- chronic overt= slower depletion => hypercoagulable state (increased clotting problems)
2
Q
Pathophysiology of DIC
A
- endothelial damage => releases tissue factor => activates clotting cascade
- activates thrombin => depletes platelets/ clotting factors => activates fibrolytic processes
- bleeding into subcutaneous tissue, skin, mucosal membranes
- fibrin (fibrinolysis) => occludes blood vessels => haemolytic anaemia + ischaemic end organ failure
Chronic DIC - process happens at a slower rate and compensatory processes => less bleeding + hypercoagulable state
3
Q
Causes of DIC
A
- INFECTION (gram-ve sepsis)
- major trauma
- surgery
- Obstetric causes (pre-eclampsia, missed misscarriage, placental abruption, amniotic emboli)
- Malignancy (acute promyelocytic leukaemia => acute DIC, lung/liver/ GI => chronic DIC)
- haemolytic transfusion reaction
- severe liver disease
- aortic aneurysm
4
Q
Symptoms + signs of DIC
A
Underlying disease: sepsis, preganacy, cancer
Acute DIC: bleeding
- nose bleeds
- petechiae, purpura, ecchymoses
- respiratory distress
- signs of shock (hypotension, tachycardia)
- anaemia
Chronic DIC: clottng problems
- DVT signs (swollen leg, SOB)
- arterial thrombosis
- anaemia
5
Q
Investigations for DIC
A
- Bloods
- FBC- low platelets, low Hb (anaemia)
- LFTs
- Clotting
- prolonged APTT/PT
- low fibrinogen
- high fibrin degradation product/D-dimer (indication of clot formation)
- Blood film: schistocytes (damaged RBC- damaged endothelium, haemolytic anaemia)
6
Q
Management for DIC
A
Acute (use severity score- PT, prothrombin, D-dimer)
- low bleeding risk => treat underlying condition
- high bleeding risk (>5) => treat underlying condition +
- platelet transfusion
- FFP transfusion (replace clotting factors, fibrinogen, plasma proteins, anticoagulant proteins)
Chronic (low bleeding risk)
- treat underlying cause
- heparin (anticoagulant)
+/- transexamic acid = antifibrinolytic (for hyperfibrinolysis)
7
Q
define Haemophillia
A
inherited clotting disorder (deficiency of clotting factors) causing XS deep bleeding and bruising
8
Q
Types of haemophillia
A
- A (MOST COMMON)- deficiency of factor 8
- B - deficiency of factor 9
- C (RARE)- deficiency of factor 11
- aquired = autoantibodies against factor 8
A=> usually caused by inversion of factor 8 gene on X-chromosome
9
Q
Inheritance pattern of haemophillia A/B
A
X-linked recessive
- Risk factors: FHx of haemophillia, more common in males
- females are usually carriers (can be symptomatic)
10
Q
Symptoms + signs of haemophillia
A
- swollen + painful joints (haemarthrosis- bleeding into joints)
- haematoma- painful bleeding into. muscle
- XS bruising
- haematuria
- nerve palsies (haemotomas compressing on nerves)
- pallor (anaemia)
- symptoms since birth/ after trauma/ after surgery
Females (carriers) => severe bleeding after trauma/ surgery or menorrhagia (heavy period bleeding)
11
Q
Investigations for haemophillia
A
- prolonged APTT
- Plasma factor 8/9/11 assay (diagnostic)
To exclude other causes:
- FBC - low Hb (if prolonged bleeding) + rule out thrombocytopenia
- LFTs (look at ALT/AST => liver disfunction => raised PT/APTT)
- Von willebrand studies => to exlcude VWD
- PT time - to look at extrinsic pathways + common
Imaging (to look at location of bleeding)
- Head CT/MRI - intracranial haemorrage
- Neck CT/MRI- bleeding in airway
- Abdo CT/ USS - lower GI bleeding
- Endoscopy - look at bleeding
- X-rays - to look at bone profile (malignancy)
12
Q
Management of haemophillia
A
Severe bleeding
- RESUS (A=>E) IV fluids
- Replace missing factor (8/9)
- Anti-fibrinolytics (aminocaproic acid/ transexamic acid)
Can give bypassing agents (recombinant FIIa + FVIII inhibitor bypasssing fraction) => to bypass coagulation cascade and generate thrombin => clotting
Mild Haemophillia A
- desmopressin (increases FVIII levels)??
- anti-fibrinolytics
- FVIII concentrate
13
Q
define anaemia
A
low Hb concentration due to:
low red cell mass (increased destruction/reduced production)
increased plasma volume
<135g/L M
<115g/L F
14
Q
symptoms of anaemia
A
fatigue
dyspnoea
faintness
palpitations
headache
tinnitus
anorexia
15
Q
symptom of anaemia if pre-existing coronary artery disease
A
angina
16
Q
signs of anaemia
A
may be absent even in severe anaemia
pallor
tachycardia
flow murmurs (ejection-systolic loudest over apex)
cardiac enlargement
retinal haemorrhages
heart failure in later stages
17
Q
first step in diagnosis of anaemia and type of anaemia
A
assess MCV
18
Q
causes of microcytic anaemia
A
iron deficiency anaemia
thalassaemia
sideroblastic anaemia
19
Q
when to suspect thalassaemia
A
if MCV is too low for Hb level and red cell count is raised
20
Q
in thalassaemia and sideroblastic anaemia, be aware that
A
there is iron accumulation
tests will show increased serum iron/ferritin
low total iron binding capacity
21
Q
causes of normocytic anaemia
A
acute blood loss
anaemia of chronic disease (reduced MCV)
bone marrow failure
renal failure
hypothyroidism (increased MCV)
haemolysis (increased MCV)
pregnancy
22
Q
when to suspect marrow failure
A
reduced WCC or platelets in normocytic anaemia
23
Q
causes of macrocytic anaemia
A
B12/folate deficiency
alcohol excess/liver disease
24
Q
suspect haemolytic anaemia if
A
reticulocytosis, mild macrocytosis
decreased: haptoglobin
increased: bilirubin, LDH, urobilinogen
mild jaundice
no bilirubin in urine
25
does anaemia require blood transfusion?
no if Hb\>70g/L
may be indicated in acute anaemia if Hb\<70g/L
**vital** in anaemia with heart failure
26
blood transfusion for anaemia with heart failure
raise Hb to 60-80g/L slowly
10-40mg furosemide IV/PO
do not mis with blood
check for signs of worsening overload (raised JVP, basal crackles)
27
causes of iron deficiency anaemia
blood loss
malabsorption
hookworm
poor diet/poverty in children/babies
28
signs of chronic iroin deficiency anaemia
koilonychia
atrophic glossitis
angular cheilosis
post-cricoid webs
29
testing for iron deficiency anaemia
blood film
coeliac serology - if negative and no menstruation, urgent gastroscopy and colonoscopy
stool microscopy if revent travel
30
blood film of iron deficiency anaemia
microcytic, hypochromic anaemia
anisocytosis and poikilocytosis
decreased: MCV, MCH, and MCHC
decreased ferritin, increased transferrin
31
NB ferritin is
an acute phase protein and increased with inflammation
32
treatment of iron deficiency anaemia
treat the cause
ferrous sulfate 200mg/8hrs for at least 3 months after Hb normalises
IV iron only if oral route impossible/ineffective
33
reasons why IDA fails to respond to iron replacement
patient compliance
functional iron deficiency in chronic renal failure
malabsorption/GI disturbance
anaemia of chronic disease
misdiagnosis
34
causes of anaemia of chronic disease
chronic infection
vasculitis
rheumatoid
malignancy
renal failure
35
pathophysiology of aneamia of chronic disease
poor use of iron in erythropoeisis
cytokine induced shortening of RBC survival
decreased production of and response to erythropoeitin
36
tests for anaemia of chronic disease
FBC
blood film
B12 and folate
TSH
tests for haemolysis
37
ferritin in anaemia of chronic disease
normal
increased in mild normocytic/microcytic anaemia
38
treatment of anaemia of chronic disease
treat underlying cause
erythropoeitin
IV iron
hepcidin inhibitors
inflammatory modulators
39
sideroblastic anaemia
ineffective erythropoeisis
increased iron absorption
iron laoding in marrow +/- haemosiderosis
40
suspect sideroblastic anaemia if
microcytic anaemia not responding to iron
41
define polycythaemia
increased RBC concentration and increased Hb concentration than normal
1. relative= low plasma volume + normal RBC conc.
2. absolute = increased RBC conc.
42
causes of absolute polycythaemia (increased RBC)
Primary
* polycythaemia rubra vera (increased clonal proliferation of myeloid stem cells =\> increased RBC =\> increased Hb conc.) ***JAK2 mutation***
Secondary
1. appropriate increase in EPO- chronic hypoxia (Chronic lung disease/ high altitudes/ obstructive sleep apnoea)
2. inappropriate increase in EPO- athletes use illegal EPO, renal/hepatocellular carcinomas, fibroids (benign tumours in uterus)
43
causes of relative polycythaemia (low plasma volume, RBC normal)
* acute- dehydration
* chronic- obesity, hypertension, smoking, high alcohol
* Gaisbock's syndrome - young male smokers + hypertension =\> low plasma volume
44
Presenting symptoms of polycythaemia
\*hyperviscosity (thick blood)
* chest/abdominal pain
* headaches
* tiredness
* **red skin**
* blurred vision
* tinitus
* **gout -** joint stiffness/pain/swelling
Polycythaemia vera
* bruising
* **pruitus after hot bath**
* burning sensation on fingers/toes (erythromelalgia)
* tummy pain from splenomegaly
* night sweats
* Risk factors: \>40, PMHx of **thrombosis**, haemorrhage, Budd-Chiari, FHx of polycythaemia vera,
45
examination findings of polycythaemia
Inspection:
* plethora (red complexion)
* scratch marks from itching
* redness of conjuctiva
* hypertension
Palpation
* splenomegaly (75%)
* abdominal masses (renal/hepatic/uterine tumours =\> secrete EPO)
46
Investigations for polycythaemia
General polycythaemia
* FBC- high Hb, high haematocrit, low MCV
* LFTs - abnormal = secondary polycythaemia
* U&Es
* serum EPO
* serum ferritin
* JAK2 mutation
* abdominal US - splenomegaly
Polycythaemia rubra vera
* **high Hb, high haematocrit**, high RBC
* **High WCC**
* **high platelets**
* low serum EPO
* JAK2 mutation
* bone marrow biopsy -erythoid hyperplasia + raised megakaryocytes
Secondary polycythaemia
* **high serum EPO**
* exclude chronic lung disease/ hypoxia (O2 sats/ CXR)
* CT scan to check for EPO tumours
47
management for polycythaemia
Conservative: (GP)
* address factors causing low plasma volume (obesity, hypertension, smoking, alcohol)
* manage CVD risk factors (hyperlipidemia, diabetes, hypertension, smoking)
Medical: (hospital)
* Polycythaemia vera =\> **VENESECTION** (removal of blood- target haemocrit \<0.45) + **aspirin**
\*if high platelet/ disease progression =\> pharmalogical cytoreductive therapy
48
Severe complications of polycythaemia
* DVT- red, swollen, painful legs,
* PE - breathlessness, haemoptysis, dizzy/lightheaded
49
define pancytopenia
* anaemia- low RBC
* leucopenia- low WCC
* thrombocytopenia- low platelets
50
Causes of pancytopenia
Central (bone marrow not producing cells)
* nutritional deficiencies (B12/folate- needed to make new cells)
* Poor absorption of nutrients (alcohol, malabsorption, tapeworm)
* Bone marrow failure
1. viral infections (EBV, HIV, hepatitis C, parvovirus B19)
2. cancers (lymphoma/leukaemia/multiple myeloma)
3. chemotherapy (*usually for cancer treatment so unless severe symptoms will not be stopped)*
4. genetic - Fanconi's anaemia
Peripheral (increased destruction of cells)
* autoimmune (RA, SLE)
* splenic sequestration due to alcoholic liver cirrhosis, HIV, TB, malaria
\*cells pooled and trapped in spleen =\> destroyed
51
presenting symptoms of pancytopenia
symptoms can vary
* anaemia (low O2)- SOB, tiredness/fatigue, chest pain, pale
* low WCC- increased infection risk (fever)
* low platelets - easy bruising, bleeding more easily/difficulty stopping bleeding
Other:
* dizziness
* paler than usual
* rashes
* ulcers
* weakness
* fast HR - palpitations
52
Emergency presentations of pancytopenia (need emergency hospital admisison)
* loss of consciousness
* seizures
* confusion
* significant blood loss
* SOB
53
Investigations for pancytopenia
1. Bloods:
* FBC- low RBC/WCC/platelets
* serum B12/folate
* LFTs
* TFTs
* autoantibodies
* test for infections (HIV-nucleic acid tests /TB)
2. Peripheral Blood smear
3. Bone marrow aspiration + biopsy (diagnose cause)
54
Management of pancytopenia
treat cause:
* nutritional supplements (B12/folate)
* treat infections (HIV- ART, TB- ABs)
* stop drugs causing damage
* immunosuppression (for autoimmune conditions)
More severe symptoms:
* stem cell transplant
* bone marrow transplant
* transfusions (if very low cell counts)
* broad-spectrum antibiotics (WCC \<500/ml)
55
Complications of pancytopenia
* increased infection risk (broad spectrum antibiotics)
* life threatening anaemia (transfusions)
* bleeding
* tumour lysis syndrome (ppl with chemo treatment =\> causes metabolic disturbance)
56
define leukaemia
cancer of the blood/ bone marrow
57
types of leukaemia
* acute myeloid- increase in myeloblasts =\> reduced RBC/WCC/platelets
* acute promyeocytic (aggressive AML)
* acute lymphoid- increase in lymphoblasts =\> reduced lymphocytes (childhood associated)
* chronic myeloid- increase in mature cells (translocation -9:22 BCR-ABL fusion gene)
* chronic lymphoid
58
Risk factors for leukaemia
* AML- increasing age, DOWN's syndrome, anti-cancer drugs
* ALL- children \<6, irradiation/influenza/genetics
* CML- genetic philadelpha chromosome (9:22)
* CLL- genetic, M\>F
59
symptoms +signs of acute leukaemia
bone marrow failure: anaemia, bleeding, infections (neutropenia)
tissue infiltration:
* Acute myeloid: swollen gums, mild splenomegaly
* Acute lymphoid: lymphadenopathy, swollen testes, hepatosplenomegaly (childhood leukaemia)
60
sign + symptoms of chronic leuakaemia
\*50% asymptomatic
Chronic myeloid (proliferation of mature cells -RBCs, WCC, platelets)
* massive splenomegaly (time to develop)
* hyperviscosity (thick blood- thrombotic events)
* hypermetabolic symptoms (FLAWS)
Chronic lymphoid
* non-tender lymphadenopathy
* some bone marrow failure symptoms
61
Investigations for leuakaemia
1. Bloods:
* FBC - WCC, RBC, platelets
* LDH - tumour marker
* Blood smear
2. Bone marrow biopsy
* auer rods- AML
* \>20% abnormal lymphoblasts - ALL
* smudge cells - CLL
3. Immunophenotyping (chromosomes), CXR
62
Management of leukaemia
1. Chemo (methotrexate)
2. Bone marrow transplant
63
define lymphoma
cancer of lymph nodes/lymphatic tissue
64
Types of lymphoma
1. Hodgkin's lymphoma
2. Non-hodgkin's lymphoma
* Burkitt's lymphoma
65
Risk factors for lymphoma
* **EBV association**
* non-Hodgkinn's: increasing age, EBV, HIV, SLE, sjoren's
66
Symptoms + signs of lymphoma
* **painless enlarging neck lump**
* FLAWS - weight loss, fatigue, night sweats
* Hodgkin's - painful when drinking alcohol, non-tender lymphadenopathy, \>FLAWS
* Non-Hodgkin's - organ symptoms (rashes, hepatosplenomegaly, headaches)
67
Investigations for lymphoma
Lymph node biopsy: (diagnostic)
* reed-sternberg cells- Hodgkin's
* starry sky apprearance - Burkitt's
68
What system is used to stage lymphomas?
Ann- Arbor
69
management for lymphoma
* chemotherapy (first line)
* radiotherapy
* immunotherapy (monoclonal antibodies)
70
define multiple myeloma
cancer of plasma cells =\> increased monoclonal immunoglobulin production
71
risk factors for myeloma
* \>70
* Afro-carribean
* agricultural work
* HIV
* ionising radiation
72
signs + symptoms of multiple myeloma (CRAB)
* Calcium (high)- bones, stones, abdominal groans, psychic moans
* Renal impariment (worse prognosis)
* Anaemia- due to overcrowding of plasma cells
* Bone lesions (back/rib pain)- cell signalling activates osteoclasts
73
Investigations for mutliple myeloma
1. Bloods:
* FBC
* Ca2+
* U&Es
* ESR/CRP
* ALP (normal, abnormal in bone cancer)
2. Blood film:
* rouleaux formation (protein/immunoglobulin clumped together like a stack of coins)
3. Electrophoresis
* bence-jones proteins (monoclonal IgG/ IgA)
4. Bone marrow aspirate/biopsy
* increased plasma cells (\>10%)
74
management for multiple myeloma
* chemotherapy
* bone marrow transplant
75
define sickle cell disease
* group of inherited diseases with a mutated beta-globin chain (HbS) which polymerise when deoxygenated so RBC becomes sickle shaped.
* Gene = Autosomal recessive
* Sickle cell trait- Hb AS (carriers of the disease)
* Sickle cell anaemia - Hb SS
76
symptoms of sickle cell disease
* usually diagnosed on **newborn screening (heel prick test)**
* signs of haemolysis (jaundice, pallor, tachycardia)
* splenic sequestration (pallor, tachycardia)
* in children swollen painful joints, dactylitis (sausage fingers)
* in adults mainly complications/ **crisis**
77
symptoms of sickle cell criss
* **severe pain**
* **infection**
* **anaemia**
* stroke/pripaism (prolonged erection)
* Hx of previous crisis
78
management of sickle cell disease
* refer if signs of crisis
* patient advice - avoid triggers (exercise, cold), increase fluids, distraction techniques
* follow care plan/ prescribe paracetomol/ibuprofen/ dihydrocodeine (severe pain)
* empirical antibiotics if signs of infection/fever
Severe episodes:
* psychological support
* elective blood transfusions (for severe anaemia)
* hydroxycarbamide- treat symptoms
* surgery
* **stem cell transplant** (curative/ rarely done)
79
prevention of complications from sickle cell
* vaccinations - pneumonoccal, influenza, meningitis
* malaria prophylaxis
* penicillin prophylaxis
80
advice for sickle cell carriers
* usually asymptomatic
* still at risk of vaso-occlusion (high altitudes, scuba diving, inform anaesthesist)
* malaria prophylaxis
* genetic counselling (kids risk of having it)
81
complications of sickle cell disease
Acute
* **sickle cell crisis**
* chest infections
* osteomyelitis
* pripaism
* AKI
* neurological complications
* strokes/TIA
Chronic
* leg ulcers
* hepatobilliary issues
* sickle lung
* pulmonary hypertension
* gallstones
* eye complications (most serious)
