Haem Flashcards
What is graft versus host disease
Occurs when T cells in the donor tissue (the graft) mount an immune response toward recipient (host) cells.
Multi-system complication of allogeneic bone marrow transplantation
Diagnosis criteria for GVHD
The transplanted tissue contains immunologically functioning cells
The recipient and donor are immunologically different
The recipient is immunocompromised
Risk factors for graft versus host disease
Poorly matched donor and recipient (particularly HLA)
Type of conditioning used prior to transplantation
Gender disparity between donor and recipient
Graft source (bone marrow or peripheral blood source associated with higher risk than umbilical cord blood)
Definition of acute GVHD
Is classically defined as onset is classically within 100 days of transplantation
What is chronic GVHD
May occur following acute disease, or can arise de novo
Classically occurs after 100 days following transplantation
Has a more varied clinical picture: often lung and eye involvement in addition to skin and GI, although any organ system may be involved
Signs and symptoms of acute GVHD
Painful maculopapular rash (often neck, palms and soles), which may progress to erythroderma or a toxic epidermal necrolysis-like syndrome
Jaundice
Watery or bloody diarrhoea
Persistent nausea and vomiting
Can also present as a culture-negative fever
Signs and symptoms of chronic GVHD
Skin: Many manifestations including poikiloderma, scleroderma, vitiligo, lichen planus
Eye: Often keratoconjunctivitis sicca, also corneal ulcers, scleritis
GI: Dysphagia, odynophagia, oral ulceration, ileus. Oral lichenous changes are a characteristic early sign
Lung: my present as obstructive or restrictive pattern lung disease
IX for GVHD
LFTs may demonstrate cholestatic jaundice. Hepatitis screen/ultrasound may be useful to exclude other causes
Abdominal imaging may reveal air-fluid levels and small bowel thickening (‘ribbon sign’)
Lung function testing
Biopsy of affected tissue may aid in diagnosis if there is uncertainty
Mx of GVHD
Intravenous steroids are the mainstay of immunosuppressive treatment in severe cases of acute GVHD.
Extended courses of steroid therapy are often needed in chronic GVHD and dose tapering is vital.
Second-line therapies include anti-TNF, mTOR inhibitors and extracorporeal photopheresis
What is haemochromatosis
autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation
early presenting features of haemochromatosis
early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)
Presentation of haemochromatosis
‘bronze’ skin pigmentation
diabetes mellitus
liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)
cardiac failure (2nd to dilated cardiomyopathy)
hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)
arthritis (especially of the hands)
Reversible complications of haemochromatosis
Cardiomyopathy
Skin pigmentation
Irreversible complications of haemochromatosis
Liver cirrhosis**
Diabetes mellitus
Hypogonadotrophic hypogonadism
Arthropathy
IX - haemochromatosis
general population: transferrin saturation is considered the most useful marker. Ferritin should also be measured but is not usually abnormal in the early stages of iron accumulation
testing family members: genetic testing for HFE mutation
Typical iron study profile in patient with haemochromatosis
transferrin saturation > 55% in men or > 50% in women
raised ferritin (e.g. > 500 ug/l) and iron
low TIBC
Mx of haemochromatosis
Venesection is the first-line treatment
monitoring adequacy of venesection: transferrin saturation should be kept below 50% and the serum ferritin concentration below 50 ug/l
desferrioxamine may be used second-line
What do joint x-rays usually show in haemochromatosis
chondrocalcinosis
Classification of blood product transfusion complications
immunological: acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis
infective
transfusion-related acute lung injury (TRALI)
transfusion-associated circulatory overload (TACO)
other: hyperkalaemia, iron overload, clotting
What is a non-haemolytic febrile reaction
Thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage
Features of non-haemolytic febrile reaction and mx
Fever, chills
mx - Slow or stop the transfusion
Paracetamol
Monitor
Features of acute haemolytic reaction
ABO-incompatible blood e.g. secondary to human error
Fever, abdominal pain, hypotension
Mx of acute haemolytic reaction
Stop transfusion
Send blood for direct Coombs test(repeat typing and cross match)
Supportive care(fluids resus)
What is TRALI
Transfusion-related acute lung injury (TRALI)
Characterised by the development of hypoxaemia / acute respiratory distress syndrome within 6 hours of transfusion
Features of TRALI
hypoxia
pulmonary infiltrates on chest x-ray
fever
hypotension
What causes TRALI
Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood
Mx of TRALI
Stop transfusion Supportive care(resus)
What is TACO
A relatively common reaction due to fluid overload resulting in pulmonary oedema. As well as features of pulmonary oedema the patient may also by hypertensive, a key difference from patients with TRALI.
Mx of TACO
Slow or stop transfusion
Consider intravenous loop diuretic (e.g. furosemide) and oxygen
Transfusion threshold for patients without ACS
70 g/L
Transfusion threshold for patients with ACS
80 g/L
Transfusion target for patients without ACS
70-90 g/L
Transfusion target for patients with ACS
80-100 g/L
How quick are RBC units transfused in a non-urgent scenario
over 90-120 mins
Risk factors Hodgkin’s lymphoma
HIV
Epstein-Barr Virus
Autoimmune conditions such as rheumatoid arthritis and sarcoidosis
Family history
Presentation of Hodgkin’s lymphoma
Lymphadenopathy is the key presenting symptom.
The enlarged lymph node or nodes might be in the neck, axilla (armpit) or inguinal (groin) region.
They are characteristically non-tender and feel “rubbery”.
Some patients will experience pain in the lymph nodes when they drink with alcohol.
Symptoms of Hodgkin’s lymphoma
Fever
Weight loss
Night sweats
Other symptoms can include:
Fatigue Itching Cough Shortness of breath Abdominal pain Recurrent infections
IX for Hodgkin’s lymphoma
Lactate dehydrogenase (LDH) is a blood test that is often raised in Hodgkin’s lymphoma but is not specific and can be raised in other cancers and many non-cancerous diseases.
Lymph node biopsy is the key diagnostic test.
CT, MRI and PET scans can be used for diagnosing and staging lymphoma and other tumours
Lymph node biopsy findings in hodgkin’s lymphoma
The Reed-Sternberg cell is the key finding from lymph node biopsy in patients with Hodgkin’s lymphoma.
They are abnormally large B cells that have multiple nuclei that have nucleoli inside them.
This can give them the appearance of the face of an owl with large eyes.
Staging system used in lymphomas
The Ann Arbor staging system is used for both Hodgkins and non-Hodgkins lymphoma. The system puts importance on whether the affected nodes are above or below the diaphragm.
Mx of Hodgkin’s lymphoma
The key treatments are chemotherapy and radiotherapy. The aim of treatment is to cure the condition. This is usually successful however there is a risk of relapse, other haematological cancers and side effects of medications.
Risks of chemotherapy in Hodgkin’s lymphoma
Leukaemia
Infertility
Risks of radiotherapy in Hodgkin’s lymphoma
Radiotherapy creates a risk of cancer, damage to tissues and hypothyroidism.
Examples of non-hodgkin’s lymphoma
Burkitt lymphoma
MALT lymphoma
Diffuse large B cell lymphoma
What are burkitt lymphomas associated with
associated with Epstein-Barr virus, malaria and HIV
What is a MALT lymphoma
MALT lymphoma affects the mucosa-associated lymphoid tissue, usually around the stomach. It is associated with H. pylori infection.
How does a diffuse large B cell lymphoma usually present
Diffuse large B cell lymphoma often presents as a rapidly growing painless mass in patients over 65 years.
Risk factors for non-hodgkin’s lymphoma
HIV Epstein-Barr Virus H. pylori (MALT lymphoma) Hepatitis B or C infection Exposure to pesticides and a specific chemical called trichloroethylene used in several industrial processes Family history Autoimmune diseases(SLE)
Mx of non-hodgkin’s lymphoma
Management involves a combination of treatments depending on the type and staging of the lymphoma:
Watchful waiting Chemotherapy Monoclonal antibodies such as rituximab Radiotherapy Stem cell transplantation
What are B symptoms of Hodgkin’s lymphoma and what do they imply
‘B’ symptoms imply a poor prognosis
weight loss > 10% in last 6 months
fever > 38ºC
night sweats
Mutation associated with burkitt’s lymphoma
Burkitt’s lymphoma is associated with the c-myc gene translocation, usually t(8:14).
Microscopy findings in burkitt’s lymphoma
‘starry sky’ appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
What might be present in a gastric MALT lymphoma
Paraproteinaemia may be present
Complications of NHL
Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia
Superior vena cava obstruction
Metastasis
Spinal cord compression
Complications related to treatment e.g. Side effects of chemotherapy
What is anisocytosis
Anisocytosis refers to a variation in size of the red blood cells. These can be seen in myelodysplasic syndrome as well as some forms of anaemia.
What are target cells
Target cells have a central pigmented area, surrounded by a pale area, surrounded by a ring of thicker cytoplasm on the outside. This makes it look like a bull’s eye target. These can be seen in iron deficiency anaemia and post-splenectomy.
What are Heinz bodies
Heinz Bodies are individual blobs seen inside red blood cells caused by denatured globin. They can be seen in G6PD and alpha-thalassaemia.
What are Howell-jolly bodies
Howell-Jolly bodies are individual blobs of DNA material seen inside red blood cells. Normally this DNA material is removed by the spleen during circulation of red blood cells.
They can be seen in post-splenectomy and in patients with severe anaemia where the body is regenerating red blood cells quickly.
What are reticulocytes
Reticulocytes are immature red blood cells that are slightly larger than standard erythrocytes (RBCs) and still have RNA material in them. The RNA has a reticular (“mesh like”) appearance inside the cell.
It is normal to have about 1% of red blood cells as reticulocytes. This percentage goes up where there is rapid turnover of red blood cells, such as haemolytic anaemia. They demonstrate that the bone marrow is active in replacing lost cells.
What are schistocytes
Schistocytes are fragments of red blood cells. They indicate the red blood cells are being physically damaged by trauma during their journey through the blood vessels.
What might the presence of schistocytes indicate
They may indicate networks of clots in small blood vessels caused by haemolytic uraemic syndrome, disseminated intravascular coagulation (DIC) or thrombotic thrombocytopenia purpura. They can also be present in replacement metallic heart valves and haemolytic anaemia.
What are sideroblasts
Sideroblasts are immature red blood cells that contain blobs of iron. They occur when the bone marrow is unable to incorporate iron into the haemoglobin molecules. They can indicate a myelodysplasic syndrome.
What are smudge cells
Smudge cells are ruptured white blood cells that occur during the process of preparing the blood film due to aged or fragile white blood cells. They can indicate chronic lymphocytic leukaemia.
What are spherocytes
Spherocytes are spherical red blood cells without the normal bi-concave disk space. They can indicated autoimmune haemolytic anaemia or hereditary spherocytosis.
Main types of myeloproliferative disorders
Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia
Chronic myeloid leukaemia
What can all myeloproliferative disorders transform into
Acute myeloid leukaemia
Genetic mutation associated with CML
t(9:22) BCR-ABL
Genetic mutation associated with PV, PMF and ET
v617F mutation –> activation of JAK2 kinase
What does activation of JAK 2 kinase result in
Stimulates erythropoietin and thrombopoietin receptors, but not GM-CSF receptors leading to a huge increase in RBCs and platelets but not WBCs
EPO and TPO levels decrease due to negative feedback from overestimation of TPO and EPO receptors
What is primary myelofibrosis
result of proliferation of the hematopoietic stem cells.
What is PV
Polycythaemia vera is the result of proliferation of the erythroid cell line
What is myelofibrosis
proliferation of the cell line leads to fibrosis of the bone marrow. The bone marrow is replaced by scar tissue. This is in response to cytokines that are released from the proliferating cells(fibroblast growth factor)
Presentation of myelproliferative disorders
Systemic sx(fatigue, weight loss, fever)
Anaemia
Splenomegaly
Portal HTN
Low platelets
Raised RBCs
Low WBCs
Key signs of PV on examination
Conjunctival plethora (excessive redness to the conjunctiva in the eyes)
A “ruddy” complexion
Splenomegaly
FBC findings - PV
Raised Hb (more than 185g/l in men or 165g/l in women)
FBC findings in primary thrombocythaemia
Raised platelet count (more than 600 x 109/l)
FBC findings in myelofibrosis
due to primary MF or secondary to PV or ET can give variable findings:
Anaemia
Leukocytosis or leukopenia (high or low white cell counts)
Thrombocytosis or thrombocytopenia (high or low platelet counts)
What might a blood film show in myelofibrosis
teardrop-shaped RBCs, varying sizes of red blood cells (poikilocytosis) and immature red and white cells (blasts).
Diagnosis of myeloproliferative disorders
Bone marrow aspiration is usually “dry” as the bone marrow has turned to scar tissue.
Testing for the JAK2, MPL and CALR genes can help guide management.
Mx of primary myelofibrosis
Mild disease - monitor
Allogeneic stem cell transplantation
Chemotherapy
Supportive management
Mx of polycythaemia vera
Venesection 1st line
Aspirin to reduce thrombus formation risk
Chemotherapy to control disease(hydroyurea)
Mx of essential thrombocythaemia
Aspirin
Chemotherapy
