List II - Less Common 'Know of' Conditions Flashcards
1
Q
What is disseminated intravascular coagulation (DIC)?
A
- Widespread activation of coagulation from release of procoagulants into circulation
2
Q
What is the clotting pathway?
A
- Intrinsic/extrinsic pathways
- Activated Xa
- Converts prothrombin to thrombin
- Converts fibrinogen to fibrin (also thrombin activated XIII to XIIIa which crosslinks fibrin)
3
Q
What is the fibrinolytic pathway?
A
- t-PA released from endothelial cells
- Converts plasminogen to plasmin
- Cleaves fibrin
4
Q
What are the causes of DIC?
A
- Malignancy - leukaemia (esp. acute promyelocytic leukaemia)
- Sepsis - meningococcal septicaemia
- Trauma
- Obstetric events - retained products (>20 wks), pre-eclampsia, placental abruption, endotoxic shock, aniotic fluid embolism, placental accreta, hydatidiform mole, acute fatty liver of pregnancy
5
Q
What is the pathophysiology of DIC?
A
- Clotting factors and platelets are consumed - increased bleeding risk
- Fibrin strands fill small vessels - haemolysing passing RBC’s
- Fibrinolysis activated
6
Q
What are the signs of DIC?
A
- Bruising, bleeding (e.g. venepunture sites), renal failure
7
Q
What are the appropriate blood investigations for DIC?
A
- FBC (low plts)
- Clotting screen (increased PT, increased APTT, low fibrinogen: correlates with severity)
- Raised D-dimer (fibrin degradation product)
- Blood film - schistocytes (haemolysed RBC’s)
8
Q
What is the approach to the management of a patient with suspected DIC?
A
- A to E assessment
- A - check patency, maintain, sit up
- B - 15L o2 NRBM
- C - IV access - bloods (as above) - replace platelets if <50 - cryoprecipitate (to replace fibrinogen) - FFP (to replace clotting factors) - activated protein C (to reduce mortality if severe sepsis/multi organ failure) - treat underlying cause
9
Q
What are the complications of DIC?
A
- Risk of death
10
Q
How can DIC be prevented?
A
- Primary prevention - acute promyelocytic leukaemia
- Give all transretinoic acid (to reduce risk of DIC)
11
Q
What is sickle cell anaemia?
A
- Auto-somal recessive condition that results in synthesis of and abnormal haemoglobin chain termed HbS
12
Q
Who is affected by SCD?
A
- More common in people of African decent
- Offers some protection against malaria
- 10% of UK Afro-Caribbean’s are carriers of HbS (i.e. heterozygous) - such people are only symptomatic if severely hypoxic
- Symptoms in homozygous people dont tend to develop until 4-6 months when the abnormal HbSS molecules take over from the fetal haemoglobin
13
Q
What is the pathophysiology of SCD?
A
- Polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6) - this decreases the water solubility of dexoy-Hb
- In the deoxygenated state the HbS molecules polymerise and cause RBC’s to sickle
- HbAS patients sickle at p02 2.5 - 4 kPa, HbSS patients at p02 5 - 6 kPa
- Sickle cells are fragile and cause infarction
14
Q
What is the investigation for SCD / how is it diagnosed?
A
- Haemoglobin electrophoresis
15
Q
How are SC crises managed?
A
- Analgesia e.g. opiates
- Rehydrate
- Oxygen
- Consider antibiotics if evidence of infection
- Blood transfusion
- Exchange transfusion e.g. if neurological complications
16
Q
What is the longer term management of SCD?
A
- Hydroxyurea
- Increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes
- Sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years
17
Q
What is haemophilia?
A
- Disorder of coagulation - meaning bleed more easily
- X-linked recessive
- Up to 30% of patients have no family history
18
Q
What is the cause of haemophilia A?
A
- Deficiency in factor VIII
19
Q
What is the cause of haemophilia B?
A
- Deficiency in factor IX (Christmas disease)
20
Q
What are the presenting clinical features of haemophilia?
A
- Haemarthroses, haematomas
* Prolonged bleeding after surgery or trauma
21
Q
What blood tests can be done for haemophilias?
A
- Prolonged APTT
* Bleeding time, thrombin time, prothrombin time normal
22
Q
Which problem can occur with treatment for haemophilia A?
A
- Up to 10-15% of patient will develop antibodies to factor VIII treatment
23
Q
What are thalassaemias?
A
- Group of genetic disorders characterised by a reduced production rate of either alpha or beta chains
24
Q
What is beta-thalassaemia trait?
A
- Auto-somal recessive condition characterised by mild hypochromic, microcytic anaemia
- Usually asymptomatic
25
What are the clinical features of thalassaemia trait?
* Mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
* HbA2 raised (>3.5%)
26
What is beta-thalassaemia major?
* Absence of beta chains
| * Chromosome 11
27
What are the clinical features of thalassaemia major?
* Presents in first year of life with failure to thrive and hepatosplenomegaly
* Microcytic anaemia
* HbA2 and HbF raised
* HbA absent
28
What is the treatment of thalassaemia major?
* Repeated transfusion - iron overload
| * s/c infusion of desferrioxamine
29
What is alpha-thalassaemia?
* Due to deficiency of alpha chains in haemoglobin
| * 2 separate alpha-globulin genes are located on each chromosome 16
30
What determines the clinical severity of alpha-thalassaemia?
* Number of alpha globulin alleles affected
- 1 or 2 alleles affected then the blood picture would be hypochromic and microcytic, but the Hb would be typically normal
- 3 alpha globulin alleles affected results in a hypochromic microcytic anaemia with splenomegaly - known as Hb H disease
- If all 4 alpha globulin alleles are affected (i.e. homozygote) then death in utero (hyrops fetalis, Bart's hydrops)
31
What is a thrombophilia?
* Blood disorder making blood more likely to clot when you dont want it to
32
What are the inherited thrombophilias?
Gain of function of polymorphisms
- Factor V Leiden (activated protein C resistance) - most common cause of thrombophilia
- Prothrombin gene mutation - second most common
Deficiences of naturally occurring anticoagulants
- Antithrombin III deficiency
- Protein C deficiency
- Protein S deficiency
33
What are the acquired thrombophilias?
* Anti-phospholipid syndrome
| * Combined oral contraceptive pill
34
What is the relative risk of VTE according to thrombophilia?
* Factor V Leiden (heterzygous)
- P 5%, VTE risk 4%
* Factor V Leiden (homozygous)
- P 0.05%, VTE risk 10%
* Prothrombin gene mutation (heterzygous)
- P 1.5%, VTE risk 3%
* Protein C deficiency
- P 0.3%, VTE risk 10%
* Protein S deficiency
- P 0.1%, VTE risk 5-10%
* Antithrombin III deficiency
- P 0.02%, VTE risk 10-20%
35
How are patients screened for VTE risk in hospital?
* VTE risk assessment tool to review risk factors including:
* Medical patients - significant reduction in mobility for 3 days or more (or anticipated to have significant reduced mobility)
* Surgical/trauma patients -
- Hip/knee replacement
- Hip fracture
- General anaesthetic and a surgical duration of over 90 minutes
- Surgery of the pelvis or lower limb with a general anaesthetic and a surgical duration of over 60 minutes
- Acute surgical admission with an inflammatory/intra-abdominal condition
- Surgery with a significant reduction in mobility
* General risk factors -
- Active cancer / chemotherapy
- Aged over 60
- Known blood clotting disorder e.g. thrombophilia
- BMI over 35
- Dehydration
- One or more significant medical comorbidities e.g. heart disease, metabolic/endocrine pathologies, respiratory disease, acute infectious disease and inflammatory conditions
- Critical care admission
- Use of hormone replacement therapy (HRT)
- Use of the combine oral contraceptive pill
- Varicose veins
- Pregnant or <6 week post partum
36
What are the different types of VTE prophylaxis?
* Mechanical
- TED / anti-embolic compression stockings - thigh or knee height
- Intermittent pneumatic compression device
* Pharmacological
- LMWH s/c injection
- Reduced doses should be used in severe renal impairment
- Unfractionated heparin
- Alternative to LMWH for patients with CKD
37
What is the advice to patients pre-surgery with regard to VTE?
* Advise women to stop taking their COCP/hormone replacement therapy 4 weeks before surgery
38
What is the advice to patients post-surgery with regard to VTE?
* Try to mobilise patients as soon as possible after surgery
| * Ensure the patient is hydrated
39
What is the post surgery VTE advice for patients who have had elective hip surgery?
* LMWH for 10 days followed by aspirin (75mg or 150mg) for a further 28 days
or
* LMWH for 28 days combined with anti-embolism stockings until discharge
or
* Rivaroxaban
40
What is the post surgery VTE advice for patients who have had elective knee surgery?
```
* Aspirin (75mg or 150mg) for 14 days
or
* LMWH for 14 days combined with anti-embolism stockings until discharge
or
* Rivaroxaban
```
41
What is the post surgery VTE advice for patients who have had fragility fractures of the pelvis, hip and proximal femur?
* NICE guidelines:
* Offer VTE prophylaxis for a month to people with fragility fractures of the pelvis, hip or proximal femur if the risk of VTE outweighs the risk of bleeding
* Choose either:
- LMWH, starting 6-12 hrs after surgery or
- Fondaparinux sodium, starting 6 hours after surgery, providing there is low risk of bleeding
42
What are the causes of severe thrombocytopenia?
* ITP
* DIC
* TTP
* Haematological malignancy
43
What are the causes of moderate thrombocytopenia?
* Heparin induced thrombocytopenia (HIT)
* Drug induced (quinine, diuretics, sulphonamides, aspirin, thiazides)
* Alcohol
* Liver disease
* Hypersplenism
* Viral infection (EBV, HIV, hepatitis)
* Pregnancy
* SLE/anti-phospholipid syndrome
* Vitamin B12 deficiency
Pseudothrombocytopenia has been reported in association with the use of EDTA as an anticoagulant
44
What are the features of immune thrombocytopenia in children?
* Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex
* Features in children (compared to adults)
- Typically more acute than adults
- Equal sex incidence
- May follow an infection or vaccination
- Usually a self limiting course over 1-2 weeks
45
What are the features of immune thrombocytopenia in adults?
* Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex
* Adults have a more chronic condition
* More common in older females
* Symptomatic patients may present as follows:
- Petechiae, purpura
- Bleeding, epistaxis
- Catastrophic bleeding e.g. intracranial is not uncommon
46
What is the management of ITP?
* First line treatment is oral prednisolone
* Pooled normal human immunoglobulin (IVIG) may also be used
* Splenectomy is now less commonly used
47
What is Evans syndrome?
* ITP in association with auto-immune haemolytic anaemia (AIHA)
48
Which condition is characterised by pancytopenia?
* Aplastic anaemia
49
What are the causes of aplastic anaemia?
* Idiopathic
* Congenital - Fanconi anaemia, dyskeratosis congenita
* Drugs - cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
* Toxins: benzene
* Infections: parvovirus, hepatitis
* Radiation
50
What is the normal range for neurophils?
* 2.0 - 7.5 * 10(9)
51
What is considered a low neutrophil count?
* <1.5 * 10(9)
Further stratified as follows:
* Mild - 1.0 - 1.5 * 10(9)
* Moderate - 0.5 - 1.0 * 10(9)
* Severe - <0.5 * 10(9)
52
What are the causes of neutropenia?
* Viral
- HIV
- EBV
- Hepatitis
* Drugs
- Cytotoxics
- Carbimazole
- Clozapine
* Benign ethnic neutropenia
- Common in black African and Afro-Caribbean
- No treatment required
* Haematological malignancy
- Myelodysplastic malignancies
- Aplastic anaemia
* Rheumatological conditions
* SLE
* RA
* Severe sepsis
* Haemodialysis
53
What are the features of neutropenic sepsis?
* Most common 7-14 days after chemotherapy
* May be defined as a neutrophil count of <0.5 * 10 (9) in a patient having anti-cancer treatment and the presence of one of the following:
- High temperature >38c
- Other signs or symptoms that are suggestive of sepsis
54
What is the prophylaxis for neutropenic sepsis?
* If it is suspected that patients are likely to have a neutrophil count of <0.5 * 10(9) as a consequence of their treatment they should be offered a fluroquinolone
55
How should neutropenic sepsis be managed?
* Antibiotics should be started immediately, do not wait for WBC
* NICE recommends starting empirical anti-biotic therapy with pipercillin with tazobactam (Tazocin) immediately
* Many units add Vancomycin if the patient has central venous access but NICE do not support this approach
* Specialist assessment to see if management can be as outpatient (or admission)
* If patients are still febrile and unwell after 48 hours an alternative anti-biotic such as meropenem is prescribed +/- vancomycin
* If patients are not responding after 4-6 days the Christie guidelines suggest ordering investigations for fungal infections e.g. HRCT rather than just starting therapy for anti-fungal blindly
* Potential role for G-CSF in selected patients
56
What is G-CSF?
* Recombinant human granulocyte-colony stimulating factors used to increase neutrophil counts in patients who are neutropenic secondary to chemotherapy or other factors
* Examples - filgrastim, perfilgrastim
57
For patients with MM, who are suitable for stem cell transplant, what should their induction therapy consist of?
* Bortezomib and Dexamethasone
58
What does an autologous stem cell transplant involve for people wit MM?
* Removal of the patients own stem cells prior to chemotherapy, which are then replaced after chemotherapy
* Different from allogenic stem cell transplantation where stem cells are sourced from HLA matching donors
* Allogenic stem cell transplantation is currently only used as part of clinical trials when treating multiple myeloma
59
What is the most common malignancy affecting children?
* Acute Lymphoblastic Leukaemia (ALL)
* Accounts for 80% of childhood leukaemia's
* Peak incidence is 2-5 years of age and boys are affected slightly more than girls
60
What are the clinical features of ALL?
Due to bone marrow failure:
* Anaemia - lethargy and pallor
* Neuropenia - frequent or severe infections
* Thrombocytopenia - easy bruising, petechiae
Others:
* Bone pain (secondary to bone marrow infiltration)
* Splenomegaly
* Hepatomegaly
* Fever in up to 50% of new cases
* Testicular swelling
61
What are the types of ALL?
* Common ALL (75%) CD10 present, pre-B phenotype
* T-cell ALL (20%)
* B-cell ALL (5%)
62
What are the poor prognostic factors for ALL?
* Age <2 yrs or >10 yrs
* WBC >20 * 10(9)/l at diagnosis
* T or B cell surface markers
* Non-caucasian
* Male sex
63
What is the most common form of leukaemia in adults?
* Chronic lymphocytic leukaemia (CLL) is caused by monoclonal proliferation of well differentiated lymphocytes which are almost always B-cells (99%)
64
What are the features of CLL?
* Often none - may be picked up as an incidental finding of lymphocytosis
* Constitutional anorexia, weight loss
* Bleeding, infections
* Lymphadenopathy more marked than chronic myeloid leukaemia
65
What are the investigations of CLL?
* FBC - lymphocytosis, anaemia
* Blood film - smudge cells (also known as smear cells)
* Immunophenotyping is the key investigation
66
What is the more common type of acute leukaemia in adults?
* Acute myeloid leukaemia (AML)
| * May occur as primary disease or following a secondary transformation of a myeloproliferative disorder
67
What are the features of AML related to bone marrow failure?
* Anaemia: pallor, lethargy, weakness
* Neutropenia: WCC may be high, functioning neutrophil levels are low leading to frequent infections
* Thrombocytopenia: bleeding
* Splenomegaly
* Bone pain
68
What are the poor prognostic factors for AML?
* >60 years
* >20% blasts after first course of chemo
* Cytogenetics: deletions of chromosome 5 or 7
69
What are the features of acute promyelocytic leukaemia M3?
* Associated with t(15:17)
* Fusion of PML and RAR alpha genes
* Presents younger than other types of AML (average = 25 years old)
* Auer rods (seen with myeloperoxidase stain)
* DIC or thrombocytopenia often at presentation
* Good prognosis
70
What is the classification of AML?
* French-American-British (FAB)
- M0 - undifferentiated
- M1 - without maturation
- M2 - with granulocytic maturation
- M3 - acute promyelocytic
- M4 - granulocytic and monocytic maturation
- M5 - monocytic
- M6 - erythroleukaemia
- M7 - megakaryoblastic
71
What is chronic myeloid leukaemia associated with?
* Philadelphia chromosome - present in more than 95%
* Due to a translocation between the long arm of chromosome 9 and 22 - t(9:22) (q34:q11)
* Results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene to form chromosome 22
* Resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
72
What is the presentation of CML?
* Usually 60-70 years
* Anaemia - lethargy
* Weight loss and sweating are common
* Splenomegaly may be marked - abdominal discomfort
* Increase in granulocyte at different stages of maturation +/- thrombocytosis
* Decreased leucocytosis alkaline phosphatase
* May undergo blast transformation (AML in 80%, ALL in 20%)
73
What is the management of CML?
* Imitinab is now first line
* Hydroxyurea
* Interferon alpha
* Allogenic bone marrow transplant
74
What is Imitinab?
* Inhibitor of the tyrosine kinase associated with the BCR-ABL defect
* Very high response rate in chronic phase CML
