Haematology Flashcards
Disseminated intravascular coagulation (DIC)
Def, cause, sx, ix, mx
inappropriate activation of the clotting cascades, resulting in thrombus formation and subsequently leading to the depletion of clotting factors and platelets
Causes:
- trauma or burns
- multi-organ failure
- sepsis
- malignancy
- APL
Sx:
- excessive bleeding
- fever
- confusion
- petechiae
- bruising
- hypotension
Ix:
- FBC
- blood film may show schistocytes due to microangiopathic haemolytic anaemia (MAHA)
- high d-dimer
- clotting profile showing increased prothrombin time (due to consumption of clotting factors), increased APTT, decreased fibrinogen (consumed due to microvascular thrombi)
Mx:
- treat underlying cause
- transfusions
- anticoagulation therapy
Epistaxis
Def, cause, ix, mx
Nose bleed that usually originates from the anterior nasal septum (Little’s area and Kiesselbach’s plexus specifically) but around 10% of cases are posterior, originating from branches of the sphenopalatine artery
Cause:
- trauma
- 02
- malignancy
- inflammation
- excess alcohol and illicit drugs
- nasal steroids
- vasculitides
- bleeding diatheses
Ix:
- mostly not required
- if significant then bloods
Mx:
- patient should sit forward (minimising bleeding into the nasopharynx), breathing through their mouth, and pinch the cartilaginous part of the nose for 10-15 minutes
- apply cold things to back of neck
- topic antiseptic (e.g. Naseptin or mupirocin) may be prescribed to reduce crusting and rebleeding
- cautery or nasal packing
- tranexamic acid if severe
Sickle cell
Def, comp, ix, mx
autosomal recessive condition in which a point mutation in the beta chain on chromosome 11 leads to the production of HbS (rather than HbA). HbS polymerises when deoxygenated leading to sickled red blood cells. These cells are fragile and sticky, causing vaso-occlusive crises leading to pain and ischaemia of vital organs
Complications:
- painful vaso-occlusive crises
- acute chest crises
- splenic infarction
- osteomyelitis
- stroke
- CKD
- gallstones
- pulmonary fibrosis
Ix:
- peak flow
- FBC may show microcytic anaemia
- blood film may show sickle cells, target cells, reticulocytes, Howell-jolly bodies
- definite dx is with haemoglobin electrophoresis +/- genetic testing
- screening
Mx:
- crisis= 02, IV fluids, transfusions
- frequent crises= hydroxycarbamide
Haemophilia
Def, cause, sx, ix, mx
Haemophilia A (more common) and B are both X-linked recessive inherited bleeding disorders, caused by deficiencies in clotting factors VIII and IX respectively, both of which are integral components of the instrinsic pathway of the coagulation cascade
Sx:
- spontaneous deep severe bleeding
Ix:
- dx with factor VII/IX assay
- bloods show high APTT
- vWF antigen in normal in A
Mx:
- desmopressin for minor bleeds in A
- major bleeds require recombinant factor VIII or IX
- antifibrinolytics (tranexamic acid) for bleeding wounds but avoid in muscle haematomas
Leukaemia
Types, sx, ix, mx
Types:
- Acute myeloid leukaemia (AML)
- Acute lymphoblastic leukaemia (ALL)
- Chronic myeloid leukaemia (CML)
- Chronic lymphocytic leukaemia (CLL)
AML:
- most common
- sx: anaemia, bleeding, infection, hepato and splenomegaly, gum hypertrophy
- ix: blasts on blood film, bone marrow biopsy is key and shows hyper cellular marrow and blasts, cytochemistry, cytogenetics, immunophenotyping to distinguish ALL
- mx: chemo, long term indwelling catheter, bone marrow transplant
ALL:
- most common childhood
- caused by the abnormal proliferation of lymphoid progenitor cells
- sx: fatigue, bleeding, bruising, infection, bone pain, lymphadenopathy, hapetosplenomegaly, CNS involvement
- ix: leucocytosis on FBC, blasts on blood film and bone marrow, immunophenotyping to find origin
- mx: chemo, CNS prophylactic agents, maintenance therapy
CML:
- most common in middle age
- sx: weight loss, tiredness, fever, splenomegaly, bleeding, gout, confusion
- ix: bloods show leucocytosis, bone marrow may show marrow hyperplasia, fibrosis, BCR–ABL/Philadelphia chromosome (reciprocal translocation between chromosomes 22 and 9)
- mx: tyrosine kinase inhibitors (eg. imatinib), hydroxycarbamide, stem cell transplantation if tyrosine kinase inhibitors dont work
CLL:
- most common in men over 60
- caused by the proliferation of functionally incompetent malignant B cells
- sx: typically asymptomatic but may have lymphadenopathy, hepatosplenomegaly, weight loss, night sweats, fever
- ix: incidental lymphocytosis, blood film shows smudge cells, immunophenotyping shows CD5 and CD23 positive, FMC negative and surface immunoglobulin weak, bone marrow biopsy which shows lymphocytic infiltration of mature lymphocytes
- staging: Binet’s system
- mx: Venetoclax (selective inhibitor of B-cell lymphoma-2, BCL-2) -Obinutuzumab (anti-CD20 monoclonal antibody) (Ven-O) or chemo with fludarabine cyclophosphamide and rituximab if TP53 not in tact
Hodgkins and non-hodgkins Lymphoma
Def, cause, types, sx, ix, mx
Hodgkins:
- malignant lymphoma characterised by the presence of Reed–Sternberg cells
- sx: alcohol induced painful cervical or supraclavicular non-tender lymphadenopathy, fever, weight loss
- types: lymphocyte predominant, nodular sclerosing, mixed picture, lymphocyte depleted
- staging:
- Stage I – involvement of a single nodal group
- Stage II – involvement of two or more nodal groups on the same side of the diaphragm
- Stage III – involvement of nodal groups on both sides of the diaphragm
- Stage IV – disseminated disease with involvement of extralymphatic organs (eg. the bones or lung)
- ix: low hb and raised LDH, Lymph node biopsy with evidence of Reed–Sternberg cells is diagnostic
- mx: most commonly used chemotherapy is ABVD = Adriamycin (doxorubicin), bleomycin, vinblastine and dacarbazine, common second-line treatment is ESHAP (etoposide, cytosine arabinoside, methylprednisolone (high dose steroids) and cisplatin)
Non-Hodgkins lymphoma:
- collective term for a variety of malignancies that impact the lymphoid system. The defining characteristic of these lymphomas is the absence of Reed-Sternberg cells
- causes: H.pylori, EBV, HIV, hep C
- types: diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL)
- sx: painless symmetrical lymphadenopathy, fever, weight loss, splenomegaly and hepatomegaly
- ix: LDH is most important and high indicates poor prognosis, uncleared red cells and left shift on blood film, biopsy to define subset
- mx: low grade NHL (radiotherapy or obinutuzumab with chemotherapy), high grade (gold standard therapy is R-CHOP chemotherapy= cyclophosphamide, doxorubicin, vincristine and prednisolone)
Myelofibrosis
Def, cause, sx, ix, mx
chronic myeloproliferative neoplasm characterized by the gradual replacement of normal bone marrow tissue with fibrous tissue
Cause:
closely associated with genetic mutations, including the Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukaemia virus oncogene (MPL) mutations
Sx:
- weight loss
- fever
- anaemia
- bleeding and bruising
- bone pain
- splenomegaly
- hepatomegaly
Ix:
- blood film typically shows tear-shaped poikilocytes and a leucoerythroblastic blood film
- high platelet and WCC
- dry tap on bone marrow aspirate
- trephine biopsy shows evidence of fibrosis, with hypercellular tissue, reduced fat space and increased reticulin staining
- high urate and LDH
- JAK-2 V617F is positive in 50% of cases
Mx:
- incurable generally
- allogenic stem cell transplant
- JAK-2 inhibitors (ruxolitinib)
Pancytopenia
Def, cause, sx, ix, mx
Characterised by reduction in RBC, WBC and platelets
Causes:
- leukaemia
- HIV
- TB
- SLE
- vitamin b12 and folate deficiency
- chemo or radiotherapy
- hypersplenism
Sx:
- fatigue
- weakness
- frequent infections
- easy bruising and bleeding
Ix:
- FBC
- bone marrow biopsy
Mx:
- treat underlying cause
- erythropoietin or granulocyte colony-stimulating factor
- blood transfusion if Hb <70 or <80 post MI
- bone marrow transplant
Anti-coagulation therapy
Eg, indication, side effects, contraindication, monitoring
DOAC examples:
- apixaban- Direct factor Xa inhibitor. It is excreted via the faeces
- dabigatran- Direct thrombin inhibitor. It is excreted by the kidneys
- edoxaban- Direct factor Xa inhibitor. The majority is excreted via the faeces
- rivaroxaban- Direct factor Xa inhibitor. It is excreted mainly by the liver, with some renal excretion
Indication:
- a fib
- DVT or PE
Side effects:
- haemorrhage
- anaemia
Contraindications:
- metallic heart valve
- preganancy
- breastfeeding
- liver disease
- antiphospholipid syndrome
- creatinine clearance <15 ml/min
- GI bleed or dyspepsia
Monitoring:
- creatinine
- weight
Anti-platelet therapy
Eg, indication, side effects, contraindication
Examples:
- aspirin
- clopidogrel
- ticagrelor
- dipyridamole
Indications:
- secondary prevention of CVD events
- ACS
Side effects:
- bleeding
- GI ulcers
- thrombocytopenia
- dyspnea
- headache
Contraindications:
- active bleeding
- thrombocytopenia
- allergy
- renal impairment
Polycythaemia
Def, cause, sx, ix, mx
an increase in haematocrit, red cell count, and haemoglobin concentration
Causes:
Relative (Hb is elevated secondary to low plasma volume):
- dehydration
- alcohol
- diuretics
- pyrexia
- diarrhoea and vomiting
Absolute primary (uncontrolled erythrocytosis independent of EPO):
- polycythaemia rubra vera
Absolute secondary (excess RBC driven by excess EPO)
- COPD
- renal neoplasms
- CKD
- tetralogy of fallot
Sx:
- Fatigue
- Headache
- Visual disturbances (secondary to hyperviscosity)
- Pruritus
- Erythromelalgia (a painful burning sensation in the fingers and toes)
- Arterial thrombosis (eg. myocardial infarction or stroke)
- Venous thrombosis (eg. pulmonary embolus or deep vein thrombosis)
- Haemorrhage (intracranial or gastrointestinal)- paradoxical increased bleeding risk (due to impaired platelet function)
- Increased risk of gout (caused by hyperuricaemia secondary to increased cell turnover).
- Facial redness on examination (plethora)
- Splenomegaly
- Hypertension
- Peptic ulceration
Primary specific:
- Hyperviscosity symptoms: Chest pain, myalgia, weakness, headache, blurred vision, loss of concentration
- ‘Ruddy complexion’
- Splenomegaly
Ix:
- FBC show raised haemotocrit, Hb, RBC mass, leukocytes, platelets
- low EPO
- JAK-2 mutation
- bone marrow biopsy showing hypercellular bone marrow
- high B12 in myeloproliferative disease
Mx:
- venesection
- polycythaemia rubra vera = venesection, 75mg aspirin, cytoreduction therapy with 1st line hydroxycarbamide, 2nd line ruxolitinib and 3rd line busulfan
Deep vein thrombosis (DVT)
Causes, sx, ix, mx
Risk factors for DVT can be remembered with the mnemonic THROMBOSIS:
• Thrombophilia
• Hormonal (COCP, pregnancy and the postpartum period, HRT)
• Relatives (family history of VTE)
• Older age (>60)
• Malignancy
• Bone fractures
• Obesity
• Smoking
• Immobilisation (long-distance travel, recent surgery or trauma)
• Sickness (e.g. acute infection, dehydration)
Sx:
• Unilateral erythema, warmth, swelling and pain in the affected area
• Pain on palpation of deep veins
• Distention of superficial veins
• Difference in calf circumference if the leg is affected
• This should be measured 10cm below the tibial tuberosity
• 3cm difference between the legs is significant
Ix:
- wells score (cancer, paralysis, surgery, tenderness, swollen more than 3cm, pitting oedema, history of DVT)
- D-dimer
- Doppler ultrasound
- bloods (FBC, U&E, LFT and coag screen)
Mx:
- DOACs (apixaban) as first line anti coag
- second line is LMW heparin for at least 5 days with a target INR of 2.5
- in unprovoked DVT drop anti coags after 3 months
Anaemia
Causes, sx, ix, mx
Causes:
- Blood loss
- Increased destruction (haemolytic)
- Inadequate RBC production (lack of iron, B12, folate, copper, erythropoietin and chronic inflammation)
Ix:
- FBC
- vit b12 and folate
- genetics
- Serum ferritin is acute phase reactant so can show inflammation
- Serum iron reflects iron intake so doesn’t show iron stores
Mx:
- More iron rich food
- Limit cow milk
- Dietician referral
- If menstruation contributes then mefenamic acid
- Address contributing factors
- Iron is better absorbed with vitamin c
Pathological fractures
Def, causes, sx, ix, mx
Pathological fractures are fractures that occur in diseased bone, often resulting from seemingly minor trauma that would not usually cause a fracture. Most commonly, these fractures arise from secondary tumors (metastatic), osteoporosis, Paget’s disease, and hyperparathyroidism.
Sx:
• Localized pain that may be severe and out of proportion to the injury
• An unexpected fracture after minor trauma
• Deformity at the fracture site
• Impaired function of the affected limb
Ix:
• Radiographic evaluation: To identify the fracture and any associated bony abnormalities
• Bone scans: To detect metabolic abnormalities and tumors
• Lab tests: Including serum calcium, phosphate, parathyroid hormone, and alkaline phosphatase to diagnose metabolic diseases
• Biopsy: May be necessary for the diagnosis of tumors
Mx:
• Treating the underlying disease: This may involve medications, surgery, or other therapies specific to the condition causing the fracture.
• Fracture repair: This can include immobilization, surgery, or other interventions as appropriate to the nature and location of the fracture.
Pulmonary embolism
Sx, ix, mx
Sx:
- Sudden-onset shortness of breath (the commonest symptom, present in around half of patients)
- Pleuritic chest pain
- Haemoptysis
- Symptoms of a DVT such as leg pain or swelling may be present
- Tachypnoea
- Crackles on auscultation
- Tachycardia
- Hypoxia
- Low-grade pyrexia in some
- In massive PE: - Hypotension - Cyanosis - Signs of right heart strain (e.g. a raised JVP, parasternal heave and loud P2)
Ix:
- wells score <4 then do d-dimer, >4 then do CTPA or V/Q scan
- ECG may show evidence of right heart strain
- ABG may show T1RF
- d-dimmer helpful to rule out
- CXR typically normal
- CTPA is main dx
- V/Q for those with severe renal impairment
- US Doppler
- TTE to ix right heart strain
Mx:
- LMWH or DOAC for 3 months if provoked or >3-6 months if unprovoked
- thrombosis is for massive PE (hypotension >15 mins) or embolectomy
Haemochromatosis
Def, cause, sx, ix, mx
disorder of iron metabolism resulting in excessive iron accumulation within various sites of the body
Cause:
- homozygosity for HFE C282Y on chromosome 6
Sx:
- Bronze skin
- Type 2 diabetes mellitus
- Fatigue
- Joint pain
- Sequalae of chronic liver disease/cirrhosis
- Adrenal insufficiency
- Testicular Atrophy
Ix:
- bloods: raised transferrin saturation (>55% in women and >50% in men)raised ferritin, raised iron, low TIBC
- genetic testing for HFE mutation
- MRI of brain and heart for iron deposition
- liver biopsy with pearls stain to check stores and loading
Mx:
- phlebotomy or venesection
- desferrioxamine
- avoid undercooked food
Thalassemia
Def, types, sx, ix, mx
characterised by abnormal haemoglobin production
Alpha:
- autosomal recessive
- 2 defective copies= asymptomatic
- 3 defective copies= symptomatic (microcytic anaemia, haemolysis, splenomegaly)
- 4 defective copies= incompatible with life
- sx= jaundice, fatigue and facial bone deformities
- ix= FBc showing microcytic anaemia, DNA analysis
- mx= blood transfusions and stem cell transplantation
Beta:
- autosomal recessive
- minor= asymptomatic
- major= frontal bossing, maxillary overgrowth, hepatosplenomegaly, failure to thrive
- ix= minor will show isolated microcytosis and mild anaemia, blood film shows target cells and basophillic stippling, increased RBC, Hb electrophoresis is diagnostic. Major will show profound microcytic anaemia, increased reticulocytes, blood film shows marked anisopoikilocytosis, target cells and nucleated RBCs, electrophoresis is diagnostic
- mx= blood transfusions, hydroxycarbamide, allogeneic bone marrow transplantation, iron chelation to prevent overload
Multiple myeloma
Def, sx, ix, mx
plasma cell dyscrasia characterised by abnormal clonal proliferation of post-germinal B cells (plasma cells)
Sx (CRAB HAI):
- hyperCalcaemia
- Renal impairment
- Anaemia
- Bone pathology
- Hyperviscosity (headache and visual disturbance)
- Amyloidosis
- Infection
Ix:
- FBC showing anaemia
- U+E showing raised creatinine
- x-rays, CT or MRI for skeletal survey
- Serum and/or urine electrophoresis will show a paraprotein spike (typically IgG)
- serum free light chain assay showing high levels
- bone marrow aspirate and biopsy
Mx:
- stem cell transplantation= DVTD then Autograft then DVTD consolidation then Lenalidomide maintenance. high-dose melphalan followed by autologous stem cell transplant is the preferred
- if not suitable for stem cell transplant= melphalan, prednisolone and thalidomide (MPT)
