Haematological Malignacies Flashcards
Define myelomas
Proliferation of plasma cells
- terminal cell of B lymphocyte
- release immunoglobulins - non-functioning
Features of myelomas
Bone marrow infiltration -> anaemia/thrombocytopenia
Cause bone and renal disease
Can form solid tumours of plasma cells (plasmacytomas)
Impaired immune system
Treatable but not curable
Myeloma presentation
Bones - generalised osteopenia - pathological fractures Hypercalcaemia - polyuria, polydipsia, abdo pain, constipation, lethargy, confusion Bone marrow infiltration - anaemia - thrombocytopenia - neutropenia Infections Hyperviscotisy syndrome - visual disturbance - headache - - - -
What define myeloma
Myeloma defining events S - 60% BM plasmacytosis Li - light chain ratio > 100 M - > 1 focal lesions on MRI > 5 mm Evidence of end organ damage C - calcium elevation > 2.75 R - renal impairment Cr>117 A - anaemia Hb < 100 B - bone lesion
Define haemopoiesis
Formation of blood cells from a hemopoietic stem cell
- cell isolated from blood or bone marrow can renew itself
- able to differentiate to a variety of specialised cells
Where does haemopoiesis go wrong
Loss of normal tight controls on haemopoiesis - too many cells proliferating - don't apoptose/die when should - don't differentiate (maturation arrest) Myeloid - acute myeloid leukaemia - chronic myeloproliferative neoplasms Lymphoid - acute lymphoblastic leukaemia - chronic lymphoblastic leukaemia - lymphoma
Leukaemia vs lymphoma
Leukaemia - affecting mainly bone marrow with or without released circulating neoplastic cells in blood
Lymphoma - predominantly nodal or organ-based
Define leukaemia
Cancer of stem cell line in bone marrow
Increase in number of white blood cells
Classification of leukaemia
Myeloid vs lymphoid
- depends on which lineage is involved
Acute vs chronic
- based on maturity of cells
- acute has proliferation of immature blast cells
- chronic has proliferation of more mature cells
- pace of disease faster in chronic
Define myeloproliferative neoplasms
Chronic proliferation of myeloid cells
Red = polycythaemia
Platelets = thrombocythemia
White = leukaemia (CML)
Features of bone marrow
Where blood cells develop
Mostly found in pelvis, vertebrae, ribs and sternum
Development of blood cells
Pluripotent haematopoietic stem cells
- undifferentiated cells that have the potential to become - myeloid stem cells, lymphoid stem cells and dendritic cells
Red blood cells
- develop from reticulocytes that come from myeloid stem cells
- survive up to 3 months
Platelets
- made by megakaryocytes
- lifespan of 10 days
White blood cells
- myeloid stem cells become promyelocytes
- monocytes then macrophages
- neutrophils
- eosinophils
- mast cells
- basophils
- lymphocytes come from lymphoid stem cells - become B and T cells
- B lymphocytes mature in the bone marrow and differentiate into plasma or memory B cells
- t lymphocytes mature in thymus gland and differentiate into CD4 cells (T helper), CD8 cells (cytotoxic T cells) and natural killer cells
Features of blood films
Anisocytosis - variation in size of red blood cells
- myelodysplastic syndrome as well as anaemia
Target cells - central pigmented area surrounded by pale area surrounded by ring of thicker cytoplasm
- iron deficiency anaemia and post-splenectomy
Heinz bodies - individual blobs seen inside RBC caused by denatured globin
- G6PD and alpha-thalassaemia
Howell-Jolly bodies - individual blobs of DNA material seen in RBC, normally removed by spleen
- post-splenectomy and severe anaemia
Reticulocytes - larger immature RBC, still have RNA material
- haemolytic anaemia
Schistocytes - fragments of RBCs
- haemolytic uraemic syndrome, DIC, thrombotic thrombocytopenia purpura, metallic heart valves, haemolytic anaemia
Sideroblasts - immature RBC that contain blobs of iron, occur when bone marrow unable to incorporate iron into haemoglobin
- myelodysplasic syndrome
Smudge cells - ruptured WBC, occur during process of preparing the blood film due to aged or fragile WBC
- chronic lymphocytic leukaemia
Spherocytes - spherical RBCs
- autoimmune haemolytic anaemia or hereditary spherocytosis
Define anaemia
Low level of haemoglobin
- women 120-165
- men 130-180
Causes of microcytic anaemia
TAILS
- thalassaemia
- anaemia of chronic disease
- iron deficiency anaemia
- lead poisoning
- sideroblastic anaemia
Causes of normocytic anaemia
3As and 2Hs
- acute blood loss
- anaemia of chronic disease
- aplastic anaemia
- haemolytic anaemia
- hypothyroidism
Causes of macrocytic anaemia
Megaloblastic - result of impaired DNA synthesis preventing cell from dividing normally - B12 or folate deficiency Normoblastic - alcohol - reticulocytosis - hypothyroidism - liver disease - azathioprine
Symptoms of anaemia
Fatigue SOB Headaches Dizziness Palpitations
Specific symptoms of iron deficiency anaemia
Pica - dietary cravings
Hair loss
Signs of anaemia
General - pale skin - conjunctival pallor - tachycardia - raised RR Specific - koilonychia, angular cheilitis, atrophic glossitis - iron deficiency - jaundice - haemolytic - bone deformities - thalassaemia
Ix for anaemia
Haemoglobin Mean Cell Volume (MCV) B12 Folate Ferritin Blood film
Causes of iron deficiency anaemia
Blood loss - most common in adults - menorrhagia - GI tract cancer Dietary insufficiency - most common in growing children Poor iron absorption Increased requirements during pregnancy
Features of iron deficiency
Ferritin - form of iron when deposited and stored in cells
- low suggestive of iron deficiency
- high is difficult to interpret as related to inflammation
Serum iron - varies throughout day
Total iron binding capacity - marker for how much transferrin is in blood
Transferrin saturation - good indication of total iron in body
Mx of iron deficiency anaemia
Blood transfusion
Iron infusion
Oral iron
Pathophysiology of pernicious anaemia
Autoimmune condition
Antibodies form against parietal cells or intrinsic factor preventing absorption of vitamin B12
Symptoms of B12 deficiency
Peripheral neuropathy with numbness or paraesthesia
Loss of vibration sense or proprioception
Visual changes
Mood or cognitive changes
Ix for B12 deficiency
Testing for auto-antibodies
- intrinsic factor antibody - 1st line
- gastric parietal cell antibody
Mx of B12 deficiency anaemia
Dietary deficiency - oral replacement - cyanocobalamin
Pernicious anaemia - 1mg IM hydroxycobalamin 3x weekly for 2 weeks, then every 3 months
Define autoimmune haemolytic anaemia
Antibodies created against patients RBCs
Leads to destruction of RBC
Types of autoimmune haemolytic anaemia
Warm
- more common
- haemolysis occurs at normal or above normal temperatures
- idiopathic
Cold
- antibodies attach at lower temperatures causing RBC to clump together - agglutination
-> destruction of RBC
- secondary to other conditions
- lymphoma
- leukaemia
- SLE
- EBV
- CMV
- HIVMx of autoimmune haemolytic anaemia
Blood transfusions
Prednisolone
Rituximab - monoclonal antibody against B cells
Splenectomy
Define thalassaemia
Genetic defect in protein chains that make up haemoglobin
- defects in alpha-globin -> alpha thalassaemia - chromosome 16
- defects in beta-globin -> beta thalassaemia - chromosome 11
Both autosomal recessive
Clinical features of thalassaemia
Microcytic anaemia (low mean corpuscular volume) Fatigue Pallor Jaundice Gallstones Splenomegaly Poor growth and development Pronounced forehead and malar eminences
Ix for thalassaemia
FBC - microcytic anaemia
Haemoglobin electrophoresis
DNA testing
Complications of thalassaemia
Iron overload
- faulty RBC, recurrent transfusions and increased iron absorption
Monitor serum ferritin
Mx involves limiting transfusions and iron chelation
Mx of alpha-thalassaemia
Monitoring the full blood count Monitoring for complications Blood transfusions Splenectomy may be performed Bone marrow transplant can be curative
Types of beta-thalassaemia
Minor
- one normal and one abnormal gene
- causes mild microcytic anaemia
Intermedia
- two defective genes or one defective and one deletion
- more significant microcytic anaemia
Major
- homozygous for deletion genes
- severe anaemia and failure to thrive in early childhood
- causes severe microcytic anaemia, splenomegaly and bone deformities
Define sickle cell anaemia
Genetic condition that causes sickle shaped red cells
Pathophysiology of sickle cell anaemia
Foetal haemoglobin replaced by haemoglobin A at around 6 weeks
Patients with sickle cell have abnormal haemoglobin variant S
- causes red blood cells to sickle
Autosomal recessive
Abnormal gene for beta-globin on chromosome 11
Complications of sickle cell anaemia
Anaemia Increased risk of infection Stroke Avascular necrosis in large joints such as the hip Pulmonary hypertension Painful and persistent penile erection (priapism) Chronic kidney disease Sickle cell crises Acute chest syndrome
Mx of sickle cell
Avoid dehydration and other triggers of crises
Ensure vaccines are up to date
Antibiotic prophylaxis to protect against infection with penicillin V (phenoxymethypenicillin)
Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.
Blood transfusion for severe anaemia
Bone marrow transplant can be curative
Define sickle cell crisis
Umbrella term for spectrum of acute crises related to the condition
Occur spontaneously of triggered by stresses
- infection
- dehydration
- cold
- significant life events
Mx of sickle cell crisis
Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)
Simple analgesia such as paracetamol and ibuprofen
Penile aspiration in priapism
Types of leukaemia
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
Pathophysiology of leukaemia
Genetic mutation in one of the precursor cells leads to excessive production of single type of abnormal WBC
Suppression of the cell lines -> pancytopenia
- low RBC - anaemia
- low WBC - leukopenia
- low platelets - thrombocytopenia
Epidemiology of leukaemia
Under 5 and over 45 - ALL
Over 55 - CLL
Over 65 - CML
Over 75 - AML
Presentation of leukaemia
Non-specific - need urgent FBC Fatigue Fever Failure to thrive (children) Pallor due to anaemia Petechiae and abnormal bruising due to thrombocytopenia Abnormal bleeding Lymphadenopathy Hepatosplenomegaly
Differential diagnosis of petechiae
Caused by thrombocytopenia
- leukaemia
- meningococcal septicaemia
- vasculitis
- idiopathic thrombocytopenia purpura
- non-accidental injury
Ix for leukaemia
FBC - within 48 hrs Blood film LDH - raised but not specific CXR - infection or mediastinal lymphadenopathy Lymph node biopsy Lumbar puncture - if CNS involvement CT/MRI/PET for staging and assessing
Types of bone marrow biopsy
Bone marrow aspiration - taking liquid sample full of cells Bone marrow trephine - solid core sample of bone marrow - better assessment of cells and structure Bone marrow biopsy - usually taken from iliac crest - local anaesthetic and specialist needle - samples can be examined straight away
Define Acute Lymphoblastic Leukaemia
Malignant change in one the lymphocyte precursor cells
- > acute proliferation of a single type of lymphocyte - usually B lymphocytes
- > replace other cell types created by bone marrow - pancytopenia
Epidemiology of ALL
Most common cancer in children - peaks 2-4 years Also affects adults over 45 Associated with Downs syndrome Associated with Philadelphia chromosome translocation
Features of blood film of ALL
Blast cells - large cell with very large nucleus
Define chronic lymphocytic leukaemia
Chronic proliferation of single type of well differentiated lymphocyte - usually B lymphocytes
Epidemiology of CLL
Adults over 55
Can transform into high-grade lymphoma - Richter’s transformation
Clinical features of CLL
Asymptomatic Infection Anaemia Bleeding Weight loss Can cause warm autoimmune haemolytic anaemia
Blood film features of CLL
Smear or smudge cells
- aged or fragile WCC rupture leaving a smudge on the film
Features of chronic myeloid leukaemia
3 phases - chronic - accelerated - blast Associated with Philadelphia chromosome
Feature of chronic phrase of CML
Lasts around 5 years
Often asymptomatic - patients diagnosed incidentally with raised WCC
Features of accelerated phase of CML
Occurs when abnormal blast cells take up high proportion of cells in bone marrow and blood
Patients become symptomatic, develop anaemia and thrombocytopenia and become immunocompromised
Features of the blast phrase of CML
Involves high proportion of blast cells and blood
Severe symptoms and pancytopenia
Often fatal
Features of acute myeloid leukaemia
Many different types all with slightly different cytogenetic differences and differences in presentation
Epidemiology of AML
Most common acute leukaemia in adults
Can present at any age - normally middle age onwards
Can result from a transformation from myeloproliferative disorder - polycythaemia ruby vera or myelofibrosis
Features of blood film of AML
High proportion of blast cells
- Auer rods - rods inside cytoplasm
Mx of leukaemia
Mainly chemotherapy and steroids
Allogenic stem cell transplant
Complications of leukaemia
Failure Stunted growth and development in children Infections due to immunodeficiency Neurotoxicity Infertility Secondary malignancy Cardiotoxicity Tumour lysis syndrome
Pathophysiology of tumour lysis syndrome
Causes by release of uric acid from cells that are being destroyed by chemotherapy
Uric acid can form crystals in interstitial tissue and tubules of kidneys
Mx of tumour lysis syndrome
Allopurinol or rasburicase used to reduce high uric acid levels
Define lymphomas
Group of cancers that affect lymphocytes inside lymphatic system
Cancerous cells proliferate within lymph nodes -> lymphadenopathy
Categories of lymphoma
Hodgkin’s
- specific disease
Non-Hodgkin’s
- encompasses all other lymphomas
- B cell or T cell in origin
- either low (aggressive, large cells seen) or high grade (small cells)
- high grade tumours have high mortality in first few years but then good prognosis as less likely to reoccur
Epidemiology of Hodgkin’s lymphoma
1 in 5 lymphomas
Caused by proliferation of lymphocytes
Bimodal age distribution with peaks around 20 and 75
Risk factors for Hodgkin’s lymphoma
HIV
EBV
Autoimmune conditions - RA and sarcoidosis
FHx
Clinical features of Hodgkin’s lymphoma
Lymphadenopathy - enlarged lymph nodes - neck, axilla or inguinal region - non-tender and rubbery - pain in nodes when drinking Fatigue Itching Cough Shortness of breath Abdominal pain Recurrent infections B symptoms - fever - weight loss - night sweats
Ix of lymphoma
Lactate dehydrogenase - raised in Hodgkin's but not specific Lymph node biopsy - Reed-Sternberg cells - abnormally large B cells with multiple nuclei with nucleoli inside them - owl face CT, MRI or PET for stagin
Staging of lymphoma
Ann Arbor Staging used for all lymphomas
Stage 1 - confined to one region of lymph nodes
Stage 2 - in more than one region but on same side of diaphragm
Stage 3 - affects lymph nodes both above and below the diaphragm
Stage 4 - widespread involvement including non-lymphatic organs such as lungs or liver
A - asymptomatic
B - b symptoms present
E - presence of extranodal site
Mx of Hodgkin lymphoma
Chemotherapy (ABVD - doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (DTIC)) and radiotherapy
- aim to cure
- usually successful
- risk of relapse
Side effects of mx of Hodgkin lymphoma
Chemotherapy - leukaemia - infertility Radiotherapy - cancer - damage to tissues - hypothyroidism
Types of non-Hodgkin Lymphoma
Burkitt lymphoma - associated with EBV, malaria and HIV
MALT lymphoma - affects mucosa-associated lymphoid tissue, usually around the stomach, a/w H.pylori
Diffuse large B cell lymphoma - presents as 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
Mx of follicular lymphoma
Stage 2A
- radiotherapy
- watch and wait if unable
Stage 3/4 (advanced)
- A - rituximab
- S - rituximab with chemotherapy
- cyclophosphamide, vincristine and prednisolone (CVP)
- cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)
Stem cell transplantation
Define myeloma
Cancer of the plasma cells
-> large quantities of single type of antibody being produced
Define multiple myeloma
Myeloma that affects multiple areas of the body
Define MGUS
Monoclonal Gammopathy of Undetermined Significance
Excess of a single type of antibody or antibody components without other features of myeloma or cancer
Often incidental finding in otherwise healthy person
May progress to myeloma
Define smouldering myeloma
Progression of MGUS with higher levels of antibodies or antibody components
Premalignant
Pathophysiology of myeloma
Genetic mutation causing a plasma cell to rapidly and uncontrollably multiply
Produce one type of antibodies (immunoglobulins)
One type (A, G, M, D and E) significantly abundant
- monoclonal paraprotein
- IgG more than 50% of the time
Bence Jones protein can be found in the urine of many myeloma patients
- subunit of the antibody - light chains
Complications of myeloma
Anaemia
Myeloma bone disease
Myeloma renal disease
Hyperviscocity
Features of anaemia of myeloma
Cancerous plasma cells invade the bone marrow - bone marrow infiltration
Suppression of development of other blood cell lines
- anaemia - low RBC
- neutropenia - low neutrophils
- thrombocytopenia - low platelets
Features of myeloma bone disease
Result of increased osteoclast activity and suppressed osteoblast activity
Metabolism of bone is imbalanced
- more bone reabsorbed than constructed
- cytokines released from plasma cells and stromal cells
Commonly occurs in skull, spine, long bones and ribs
- some areas of bone becomes thin - osteolytic lesions
- lead to pathological fractures
Osteoclast activity causes a lot of calcium to be released into blood
- hypercalcaemia
Development of plasmacytomas
- individual tumours made up of cancerous plasma cells
Features of myeloma renal disease
Development of renal impairment
- High levels of immunoglobulins (antibodies) can block the flow through the tubules
- Hypercalcaemia impairs renal function
- Dehydration
- Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys
Features of hyperviscocity of myeloma
Viscosity increases due to increased proteins
Leads to
- easy bruising
- easy bleeding
- reduced or loss of sight due to vascular disease
- purple discolouration to the extremities
- heart failure
4 key features of myeloma
CRAB Calcium elevated Renal failure Anaemia - normocytic, normochromic Bone lesions/pain
Risk factors for myeloma
Older age Male Black African ethnicity Family history Obesity
Ix for myeloma
Suspect in anyone over 60 with persistent bone pain, particularly back pain or unexplained fractures FBC - low WCC Calcium - raised ESR - raised Plasma viscosity - raised
Testing for myeloma
B - Bence-Jones protein - request urine electrophoresis L - serum-free light chain assay I - serum immunoglobulins P - serum protein electrophoresis Bone marrow biopsy - confirm diagnosis Imaging - whole body MRI - whole body CT - skeletal survery
Features of myeloma on x-ray
Punched out lesions
Lytic lesions
Raindrop skull
Mx of myeloma
Aim of treatment to control disease - often takes relapsing-remitting course Chemotherapy - bortezomid - thalidomide - dexamethasone Stem cell transplantation VTE prophylaxis
Mx of myeloma bone disease
Bisphosphonates - suppress osteoclast activity
Radiotherapy - improve pain
Orthopaedic surgery - stabilise bones
Cement augmentation - injecting cement into vertebral fractures/lesions to improve spine stability and pain
Complications of myeloma
Infection Pain Renal failure Anaemia Hypercalcaemia Peripheral neuropathy Spinal cord compression Hyperviscocity
Define myeloproliferative disorder
Type of bone marrow cancer
Occur due to uncontrolled proliferation of a single type of stem cell
Have the potential to progress and transform into acute myeloid leukaemia
Associated with mutations of JAK2, MPL and CALR genes
Types of myeloproliferative disorders
Primary myelofibrosis - proliferation of hemopoietic stem cells
Polycythaemia vera - proliferation of erythroid cell line
Essential thrombocythemia - proliferation of megakaryocytic cell line
Define myelofibrosis
Proliferation of cell line leads to fibrosis of bone marrow
Response to cytokines released by proliferating cells
Haematopoiesis occurs in other areas such as liver and spleen (extramedullary haematopoiesis)
-> hepatomegaly and splenomegaly -> portal hypertension
Presentation of myeloproliferative disorders
Initially asymptomatic Systemic symptoms - fatigue - weight loss - night sweats - fever Underlying complications - anaemia - except in polycythaemia - splenomegaly (abdo pain) - portal hypertension ( ascites, varices and abdo pain) - low platelets (bleeding and petechiae - thrombosis - raised RBC - low WCC (infections)
Key features of examination of polycythaemia vera
Conjunctival plethora - excessive redness
Ruddy complexion
Splenomegaly
FBC findings for myeloproliferative disorders
Polycythaemia vera - raised Hb Primary thrombocythemia - raised platelet count Myelofibrosis - anaemia - leucocytosis or leukopenia - thrombocytosis or thrombocytopenia - tear-dropped shaped RBCs, varying sized RBC (poikilocytosis) and blast cells on blood film
Ix for myeloproliferative disorders
Bone marrow biopsy
- bone marrow aspiration dry due to fibrosis
Testing for JAK2, MPL and CALR genes
Mx of primary myelofibrosis
Those with mild disease monitored
Allogenic stem cell transplantation - curative but carries risk
Chemotherapy - help control disease, improve symptoms and slow progression but not curative alone
Supportive
Mx of polycythaemia ver
Venesection - used to keep haemoglobin in normal range
Aspirin - reduce thrombosis risk
Chemotherapy - control disease
Mx of essential thrombocythaemia
Aspirin - reduce risk of thrombus formation
Chemotherapy - control disease
Features of myelodysplastic syndrome
Caused by myeloid bone marrow cells not maturing properly and producing healthy blood cells
Causes low level of blood components that originate from the myeloid cell line
- anaemia
- neutropenia
- thrombocytopenia
Increased risk of transforming into acute myeloid leukaemia
Epidemiology of myelodysplastic syndromes
More common in patients over 60
Patients who have previously had treatment with chemotherapy and radiotherapy
Clinical features of myelodysplastic syndromes
May by asymptomatic - incidentally diagnosed on FBC
Present with symptoms of
- anaemia - fatigue, pallor or SOB
- neutropenia - frequent of severe infections
- thrombocytopenia - purpura or bleeding
Ix of myelodysplastic syndromes
FBC abnormal
Blasts on blood film
Diagnosis confirmed by bone marrow aspiration and biopsy
Mx of myelodysplastic syndromes
Watchful waiting
Supportive treatment with blood transfusions if severely anaemic
Chemotherapy
Stem cell transplantation
Define thrombocytopenia
Low platelet count
Causes of thrombocytopenia
Problems with production - sepsis - B12 or folic acid deficiency - liver failure - leukaemia - myelodysplastic syndrome Problems with destruction - medications - sodium valproate, methotrexate, antihistamines, PPIs - alcohol - immune thrombocytopenic purpura - heparin-induced - haemolytic uraemic syndrome
Presentation of thrombocytopenia
Mild may be asymptomatic
Spontaneous bruising and prolonged bleeding times
- nosebleeds, bleeding gums, heavy periods, blood in urine/stools
Ddx of abnormal or prolonged bleeding
Thrombocytopenia
Haemophilia
Von Willebrand disease
DIC
Define immune thrombocytopenic purpura
Antibodies created against platelets
- destruction of platelets
- low platelet count
Mx of ITP
Prednisolone
IV immunoglobulins
Rituximab
Splenectomy
Define thrombotic thrombocytopenic purpura
Tiny blood clots develop throughout small vessels of body
- using up platelets
Pathophysiology of TTP
Problem with ADAMTS13 protein
- normally inactivated von Willebrand factor reducing platelet adhesion
Shortage of protein leads to von Willebrand factor overactivity
Clots break up RBC -> haemolytic anaemia
Mx of TTP
Referral to haematologist
Plasma exchange
Steroids
Rituximab
Pathophysiology of heparin induced thrombocytopenia
Development of antibodies against platelets in response to heparin exposure
- target platelet factor 4 - anti-PF4/heparin antibodies
Bind to platelets and activate clotting mechanisms
-> thrombosis
Breakdown of platelets
-> thrombocytopenia
Mx of heparin induced thrombocytopenia
Diagnosis by HIT antibody testing
Stop heparin
Use alternative anticoagulant
Features of von Willebrand disease
Most common inherited cause of abnormal bleeding
Manly autosomal dominant
Deficiency, absence or malfunctioning of glycoprotein von Willebrand factor
Mx of von Willebrand factor
Desmopressin - stimulates release of VWF VWF infusion Factor VIII Mx of heavy periods - tranexamic acid - mefanamic acid - norethisterone - COCP - Mirena coil - hysterectomy
Features of haemophilia A and B
A caused by deficiency of factor VIII
B caused by deficiency of factor IX
X-linked recessive - much more common in males
Presentation of haemophillia
Spontaneous haemorrhage - hemarthrosis - bleeding into muscles Presentation in neonatal/early period - intracranial haemorrhage - haematomas - cord bleeding
Ix for haemophillia
Bleeding scores
Coagulation factor assays
Genetic testing
Mx of haemophillia
Replacement of clotting factors by IV infusion
- prophylactically
- in response to bleeding
- can result in antibody formation against clotting factor - becomes ineffective
Desmopressin - stimulates release of von Willebrand factor
Antifibrinolytics
Risk factors for VTE
Immobility Recent surgery Long haul flights Pregnancy Hormone therapy with oestrogen (combined oral contraceptive pill and hormone replacement therapy) Malignancy Polycythaemia Systemic lupus erythematosus Thrombophilia
DVT presentation
Unilateral Calf or leg swelling Dilated superficial veins Tenderness to the calf (particularly over the site of the deep veins) Oedema Colour changes to the leg
Ix for VTE
Wells score D-dimer - also raised - pneumonia - malignancy - heart failure - surgery - pregnancy USS doppler of leg CTPA or VQ for PE
Mx of VTE
Initial management with LMWH
- started immediately before confirming diagnosis
Long term anticoagulation
- warfarin, NOAC (apixaban, dabigatran or rivaroxaban) or LMWH
Continue anticoagulation for
- 3 months in obvious reversible cause
- beyond 3 months is cause unclear, recurrent VTE or irreversible underlying cause
- 6 months is active cancer
Ix for unprovoked DVT
Screen for cancer - history + examination - CXR - bloods - FBC, calcium + LFTs - urine dipstick - CT abdo and pelvis in patients over 40 - Mammogram in women over 40 Antiphospholipid antibodies to check for antiphospholipid syndrome If FHx test for hereditary thrombophilias
Define Budd-Chiari syndrome
Blood clot develops in hepatic vein blocking outflow of blood
-> acute hepatitis
Features of Budd-Chiari syndrome
Abdo pain
Hepatomegaly
Ascites
Presentation of ALL
Pancytopenia
Bone pain
Mx of ALL
Multi-drug chemotherapy
Complications of CLL
Infiltration of BM
Reduction in repertoire of antibodies
Altered T cell immunity
Autoimmune phenomena - due to immune dysregulation
- AIHA
- ITP
Transformation to high grade lymphoma - Richters transformation
Mx of CLL
Not all need treatment - undergo watch and wait period
Treatable but not curable
Treated when clinically indicated
• Hb<10
• Plt<100
• Significant lymphadenopathy, massive splenomegaly
• Doubling time <6 months (time for lymphocyte count to double, only
significant once the lymphocyte count is more than 30)
• Infections
• Autoimmune phenomena
Treatment includes chemotherapy, targeted therapies such as monoclonal antibodies and tyrosine kinase inhibitors
Secondary causes of high platelets
Bleeding Iron deficiency Inflammation Infection Post-surgery Splenectomy
Secondary causes of high RBC
Chronic hypoxia Smoking Obstructive sleep apnoea Altitude Renal/hepatic tumours Congenital heart disease
Role of lymphatic system
Defence against infection
Return of tissue fluid to blood
Absorption of fats and vitamins from GI tract
Define aplastic anaemia
Failure of all lines resulting in pancytopenia
- anaemia
- thrombocytopenia
- neutropenia
Clinical features of aplastic anaemia
Anaemia
Bleeding
Infection
Ix for aplastic anaemia
FBC Reticulocyte count B12 and folate levels Infection screen LFTs and U+Es Thyroid function Bone marrow aspirate for diagnosis
Mx of aplastic anaemia
Supportive
- reduce infection risk
- treat infection aggressively
- platelet and red cell transfusions as appropriate
- ATG and ALG immunotherapy
Causes of splenomegaly
Massive - myeloproliferative disorders - CML, AML and myelofibrosis - tropical infections - malaria - HIV Moderate - myeloproliferative disorders - lymphoproliferative disorders - CLL, lymphoma - amyloidosis Mild - myelo and lymphoproliferative disorders - portal hypertension - infections - IE, EBV, viral hepatitis - haemolytic anaemia - autoimmune - SLE
