Haem fifth yr Flashcards
What is Myelodysplastic syndrome?
caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells.
Causes low levels of blood components from myeloid line: anaemia, neutropenia, thrombocytopenia
Common in its >60 and its that have previously had chemo or radiotherapy
risk of transforming to AML
blasts on blood film
Dx - bone marrow aspiration, biopsy
Tx - watchful waiting, supportive (transfusion if severely anaemic), chemo, stem cell transplantation
What is myelofibrosis?
result of proliferation of the hematopoietic stem cells. can be result of primary myelofibrosis, polycythaemia vera or essential thrombocythaemia
where proliferation of the cell line leads to fibrosis of the bone marrow. bone marrow is replaced by scar tissue. This is in response to cytokines that are released from the proliferating cells. One particular cytokine is fibroblast growth factor. This fibrosis affects the production of blood cells and can lead to anaemia and low white blood cells (leukopenia).
haematopoiesis starts to happen in other areas such as liver and spleen. (causing hepatosplenomegaly) - causes portal hypertension and SCC
can transform to AML
associated with certain gene mutations - JAK2, MP, CALR
Features of myelofibrosis?
elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom)
massive splenomegaly
hypermetabolic symptoms: weight loss, night sweats etc
Lab findings of myelofibrosis?
anaemia
high WBC and platelet count early in the disease. also leukopenia or thrombocytopenia
‘tear-drop’ poikilocytes on blood film
unobtainable bone marrow biopsy - ‘dry tap’ therefore trephine biopsy needed
high urate and LDH (reflect increased cell turnover)
Management of primary myelofibrosis?
Patients with mild disease with minimal symptoms might be monitored and not actively treated.
Allogeneic stem cell transplantation is potentially curative but carries risks.
Chemotherapy can help control the disease, improve symptoms and slow progression but is not curative on its own.
Supportive management of the anaemia, splenomegaly and portal hypertension.
What is Von Willebrands Disease?
most common inherited cause of abnormal bleeding (haemophilia)
mostly AD causes
The causes involve a deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF). There are three types based on the underlying cause and ranging from type 1 to type 3. Type 3 is the most severe.
Features of Von Willebrand Disease?
History of unusually easy, prolonged or heavy bleeding:
bleeding gums with brushing
epistaxis
heavy menstrual bleeding
heavy bleeding during surgical operations
FHx of heavy bleeding or VWD
Diagnosis of VWD?
based on a history of abnormal bleeding, family history, bleeding assessment tools and laboratory investigation
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
Tx of VWD?
Does not require day to day treatment
Management is required either in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding)
Desmopressin can be used to stimulates the release of VWF
VWF can be infused
Factor VIII is often infused along with plasma-derived VWF
Women suffering from VWD that have heavy periods can be managed with: tranexamic acid, mefanamic acid, norethisterone, COCP, mirena, hysterectomy
Summary of tumour lysis syndrome?
related to the treatment of high-grade lymphomas and leukaemias - usually triggered by chemotherapy
Patients at high risk of TLS should be given IV allopurinol or IV rasburicase immediately prior to and during the first days of chemotherapy - metabolises uric acid to allantoin which is more easily excreted by kidneys
TLS occurs from the breakdown of the tumour cells and the subsequent release of chemicals from the cell.
It leads to a high potassium and high phosphate level in the presence of a low calcium.
graded using the Cairo-Bishop scoring system
Clinical tumor lysis syndrome: laboratory tumour lysis syndrome plus one or more of the following:
increased serum creatinine (1.5 times upper limit of normal)
cardiac arrhythmia or sudden death
seizure
Summary of Immune Thrombocytopenic Purpura?
condition where antibodies are created against platelets. This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count
Children with ITP usually have an acute thrombocytopenia that may follow infection or vaccination. In contrast, adults tend to have a more chronic condition.
Sx - detected incidentally following routine bloods, petechiae, Purpura, bleeding (e.g., epistaxis), catastrophic bleeding not common
Ix - FBC (isolated thrombocytopenia), blood film, bone marrow no longer used,
Tx = oral prednisolone, IVIG (does quicker than steroids so used if active bleeding or urgent invasive procedure), Rituximab, splenectomy
The platelet count needs to be monitored
Patient education - signs of bleeding - headache, melaena,
Avoid team sports that may result in trauma
Controlling BP
Suppressing menstrual periods
Evan’s syndrome - ITP in association with autoimmune haemolytic anaemia (AIHA)
ITP resolves in around 80% of children with 6 months, with or without treatment
Summary of Thrombotic Thrombocytopenic Purpura?
where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues. It affect the small vessels so it is described as a microangiopathy.
develop due to a problem with a specific protein called ADAMTS13. This protein normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation. A shortage in this protein leads to von Willebrand factor overactivity and the formation of blood clots in small vessels.
Overlaps with haemolytic uraemia syndrome
Sx - rare, typically adult females, fever, fluctuating neuro signs (micro emboli), microangiopathic haemolytic anaemia, thrombocytopenia, renal failure
Causes - post infection (urinary, GI), pregnancy, drugs (ciclosporin, OCP, penicillin, clopidogrel, Aciclovir), tumours, SLE, HIV
Blood clots in small vessels break RBCs - leading to haemolytic anaemia
Deficiency in ADAMTS13 can be due to inherited genetic mutation or due to autoimmune disease
Tx - guided by haematologist, plasma exchange, steroids, Rituximab
Summary of Heparin Induced Thrombocytopenia?
involves the development of antibodies against platelets in response to exposure to heparin.
These heparin induced antibodies specifically target a protein on the platelets called platelet factor 4 (PF4) - anti PF4/heparin antibodies
antibodies bind to platelets and activate clotting mechanisms. causes hyperocoagulable state and leads to thrombosis. also breaks down platelets causing thrombocytopenia.
Leads to situation where patient on heparin with low platelets forms unexpected blood clots.
Dx - test for HIT antibodies
Tx - stop heparin, using alternative anticoagulant guided by specialist
What is acute intermittent porphyria?
are autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem.
The results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen.
It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40-year-olds.
AIP is more common in females (5:1)
Sx of acute intermittent porphyria?
The classical presentation is a combination of abdominal, neurological and psychiatric symptoms:
abdominal: abdominal pain, vomiting
neurological: motor neuropathy
psychiatric: e.g. depression
hypertension and tachycardia common
Ix and Tx of acute intermittent porphyria?
Ix:
classically urine turns deep red on standing
raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks)
assay of red cells for porphobilinogen deaminase
raised serum levels of delta aminolaevulinic acid and porphobilinogen
Tx:
avoiding triggers
acute attacks:
IV haematin/haem arginate
IV glucose should be used if haematin/haem arginate is not immediately available
Causes of polycythaemia?
Relative: dehydration, stress (Gaisbock syndrome)
Primary - polycythaemia rubra vera
Secondary - COPD, altitude, OSA, excessive EPO (cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids)
Differentiate between primary and secondary - red cell mass studies - In true polycythaemia the total red cell mass in males > 35 ml/kg and in women > 32 ml/kg
Features of polycythaemia vera?
pruritus - typically after a hot bath
splenomegaly
HTN
hyperviscosity - arterial thrombosis, venous thrombosis
haemorrhage - secondary to abnormal platelet function
low ESR
What is polycythaemia vera?
myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets.
mutation in JAK2
incidence peaks in 6th decade
