Haematology Flashcards

Question

Myeloma

Answer 1

Definition: Malignant plasma cells proliferation within the bone, which secrete paraproteins (monoclonal Ig’s) into blood. If tissue impairment termed “multiple myeloma”, if no tissue impairment “smouldering myeloma” Cause: Pre-symptomatic MGUS Presentation: Bone pain +/- pathological fracture + CRAB. Course is relapsing and remitting. Investigations: 1st line - Serum protein electrophoresis AND bence jones proteinuria Diagnostic – Bone marrow aspirate and trephine (>10% clonal plasma cell content) Assessing progression: Skeletal survey with MRI/CT, FBC, U+Es and cCa Treatment: Supportive measures – Hydration (3L fluid / 24 hrs), Zoledronate if hyperCa or bone protection needed, opiates and palliative RT for bone pain, RBC transfusion if symptomatic anaemia, Abx if bacterial infection Multiple myeloma – Either intensive or non-intensive chemotherapy (Difference: Intensive for more resilient patients i.e. <70 with few co-morbidities as contains autologous stem cell transplant)

Answer 2

Types: - Polycythaemia vera - Essential thrombocythaemia - Primary myelofibrosis

Answer 3

*Type of Myeloproliferative neoplasm Cell line: Red ``` Effect: • Hyperviscosity • Arterial and venous thrombosis • Elevated Hb • Splenomegaly ``` Ix: 1st line JAK2 V617F Mutation screen Risk: Hyperviscosity induced thrombosis Mx: Aspirin Venesection ie. removing blood to reduce count Chemo - hydroxyurea - increases chance of leukaemia which 5-15% of pts get.

Answer 4

*Type of Myeloproliferative neoplasm Cell line: Platelets ``` Effect: • 40-50% asymptomatic • Vasomotor symptoms • Arterial and venousthrombosis • Ischaemia and gangrene ``` Risk: Thrombosis

Answer 5

``` *Type of Myeloproliferative neoplasm Cell line: Fibroblasts Effect: Marrow failure, *splenomegaly Ix: BM aspirate -> “Dry tap” Presentation: Insidious fatigue and weight loss. Splenomegaly (due to compensatory haematopoiesis) ```

Answer 6

Definition: Autosomal recessive single nucleic acid mutation for the beta globin chain -> Produces haemoglobin (HbS) which CLUMPS on deoxygenation producing sickle shape of RBC. Lost disc flexibility so cannot pass through narrow vessels easily so gets damaged Sickling precipitators: Hypoxia, infection, acidosis, cold temp, low HbF Ix: Screening in Day 5 newborn heelprick test or Definitive diagnosis with haemoglobin electrophoresis Presentation: At 4-6 months old with chronic haemolytis anaemia (Hb 70g/l, jaundice, reticulocytosis) Complications: Acute organ VOC (At lung, brain, penis), sequestration crises, aplastic crises with parvovirus, haemolytic crisis, chronic end-organ damage (lung and spleen *inf risk w/encapsulated organisms) Managements: In crisis – Analgesia, rehydrate, o2, abx, blood transfusion, exchange transfusion if neuro complications Long term – Hydroxyurea + pneumococcal vaccine every 5 years

Answer 7

Classification: Haemophilia A – Factor VIII deficiency (more common) Haemophilia B – Factor IX deficiency Inheritance patient: X-linked recessive. Only 35% cases are inherited Presentation: Easy / prolonged bruising, haemarthrosis FHx haemophilia Ix: Coagulation screen (isolated prolonged APTT. Normal prothrombin time and fibrinogen) Management: Recombinant factor VIII and IX

Answer 8

What? Haemoglobinopathy due to faulty production of Hb in the beta or alpha chains Epidemiology Alpha thalassaemia - SE Asia, Africa and India Beta thalassaemia - Mediterranean, Middle east, Southern china, Centra/south/ SE Asia Classification: Alpha thalassaemia by number of genes present in total (3 = Silent carrier, 2 = Alpha zero trait, 1 = Haemoglobin H disease (HbH) , 0 = Hb Barts / Hydrops fetalis) Beta thalassaemia by number of genes mutated (Beta Trait = 1 gene. Intermedia = 2 gemes but still able to function. BTM = 2 genes) Presentation: BTM - Microcytic anaemia. First year of life failure to thrive and hepatospenomegaly. Ix show HbA2 and HbF rising, absent HbA Beta trait - Asymptomatic, HbA2 raised. Mild hypochromic microcytic aneamia Alpha trait - Not anaemia. Blood is microcytic and hypochromic HbH diease - Mild with mild persistent anaemia and splenomegaly Hb Barts - Miscarriage Ix: 1st line - FBC (Hb low, RBC high, MCV vvv low) and genetic testing Screening- Pregnanct women <10 weeks, newborns at heelprick on Day 5 Management of BTM If anaemic but asymptomatic --> Monitor If anaemia by symptomatic --> Repeated transfusion every 3/4 weeks, chelation to prevent Fe overload

Answer 9

Physiology: vWF normally involved in platelet adhesion to endothelium during primary haemostasis and is factor VIII carrier molecules Classifications: Type 1 (partial reduction of vWF), Type 2 (abrnomal form of vWF), Type 3 (total lack of vWF) Inheritance: Autosomal dominant (except Type 3 which is AR) Presentation: Mucosal bleeding -> Epistaxis, menorrhagia, dental bleeding, easy bruising) Ix: Coagulation screen (Slightly prolonged APTT, prolonged bleeding time, factor VIII moderately reduced Mx: Tranexamic acid, DDAVP i.e. desmopressin, factor VIII concentrate.

Answer 10

Normal physiology: - Synthesis of coag factors - Synthesis of anti-coagulant proteins (Antithrombin, protein S, protein C) - Carboxylation of Vit K dependent factors - Clearance of activated coag factors and fibrinolytic factors Pathophysiology In PRIMARY haemostasis: Bleeding due to thrombocytopaenia and platelet dysfunction Thrombosis due to elevated vWF levels In SECONDARY haemostasis: Bleeding due to reduced coag factor productions and vit K dependent factor dysfunction Thrombosis due to elevated VIII-endothelial activation, reduced protein c production and reduced fibrinogen In FIBRINOLYSIS: Bleeding due to accumulation of tPA and low alpha2 antiplasmia Thrombosis due to low plasminogen an Presentation: Bleeding or thrombosis Management: - Avoid non-essential surgery - Monitor coags - FFP (coag factor source), Cry (fibrinogen source) and platelets

Answer 11

Definition: Consumptive coagulopathy secondary to underlying disease where excessive coagulation leads to plts and clotting factors being depleted Cause: - Sepsis - Obstetric (Placental abruption, AFE, HELLP) -Immunological Rx (ABO incompatibility, transplant rejection) -Liver failure Cancer -Trauma Presentation: Clinically - Widespread clots and bleeding Lab - Coagulation screen (All times HIGH), fibrinogen low, plts low, d-dimer high, blood films show schistocytes Tx: 1st line - Treat cause and correct abnormalities (plts transfusion, FFP, cyro, recombinant activated protein C, rFactor ViIIa)

Answer 12

Definition: Immune mediated reduction of platelet count, leading to bleeding Classification: - Acute/transient form (children post infection or vaccine) - Chronic/insidious form (adults, esp mid-aged women) Presentation: - Easy bruising from minor injury - Petechiae on lower limb - If chronic, fatigue Ix: Diagnostic- Plt count (<50 = bleeding after minor injury, <20 bleeding unprovoked) and microscopy DDx: - TTP - HUS Management: Indication: Children with SEVERE presentation, ALL adults 1st line- PRED oral 2nd line - Add IV immune globulins / TPO rec agonist / immunosuppressives 3rd line - Splenectomy Life-threatening - Platelet transfusions + IV corticosteroids +/- immune globulin Prognosis: Children respond to Tx within weeks-months. Adults respond within 1 year Evan's syndrome: ITP + AIHA

Answer 13

Classification: - Warm * - Cold Cause: Idiopathic* Warm (SLE, lymphoma, SLL, methyldopa) Cold (lymphoma, mycoplasma, EBV) MEL C Presentation Warm (Extravascular haemolysis e.g. at the spleen) Cold (Intravascular haemolysis with raynaud's, acrocyanosis) DDx for haemolytic anaemia - HDN - Grp 6 PD - Valve / mechanical haemolysis - Hereditary spherocytosis - DIC - TTP - HUS - Pre-eclampsia - HELLP syndrome Investigations: 1st line - FBC (macrocytic anaemia with reticulocytosis) Diagnostic - Coombs test (with be positive for abs) Management: Indications - Not all warm types Warm type - 1st line PRED 2nd line Immunosuppressive w/ Rituximab 3rd splenectomy Cold type - Immunosuppressive w/ Rituximab Hemolytic disease of the newborn (HDN) is a blood problem in newborn babies. It occurs when your baby's red blood cells break down at a fast rate. It's also called erythroblastosis fetalis. Hemolytic means breaking down of red blood cells. Erythroblastosis means making immature red blood cells. CLL (chronic lymphocytic leukemia) and SLL (small lymphocytic lymphoma) are the same disease, but in CLL cancer cells are found mostly in the blood and bone marrow. In SLL cancer cells are found mostly in the lymph nodes. CLL/SLL is a type of non-Hodgkin lymphoma. Literally, acrocyanosis means bluish discoloration of the extremities due to decreased amount of oxygen delivered to the peripheral part.

Answer 14

Cause: - Alloimmunisation of pregnancy - Failed prophylaxis - FMH Risk to foetus: Haemolysis (risk of foetal hydrops) and bilirubinaemia (risk of kernicterus) Ix: Antenatal test - For Rh D negative mothers with indirect coombs Routine antenatal US (looking for fetal hydrops or polyhydramnios. If anemia then fetal blood sample required) Postnatal diagnosis - Cord blood sample (shows positive coombs test and ABO or Rh incompatibility) Management In utero- IV transfusion at 18 weeks with Group O- packed cells. Planned delivery at 37-38 weeks Postnatal - Depends on considiton of feotus. ranges from monitor for anaemia at 6-8 weeks --> transfusion + phototherapy --> Resus + transufiosn + temp stabilisation + Early IVIG Complications: 1. Kernicterus 2. Anaemia at 6-8 weeks 3. HvD disease 4. Infections Prevention: Anti-D ig administration to all RhD neg mothers at 28 and 34 weeks, after sensitising event or postnatally to RhD +ve neonates of Rh D negative mothers within 72 hours

Answer 15

Presentation: - Unilateral - Sub-acute onset - Erythema - Painful, esp on mobilising DDx - DVT - Arterial thrombosis - Ruptured baker's cyst - Cellulitis - Lymphatic obstruction ``` Risk factors: Acquired - Pregnancy - COCP / HRT - Cancer - CV disease - DM - Previous DVT/PE - Aviation travel - GA and surgery - APS - Obesity -Smoking ``` Inherited - FH - Inherited thrombophilia (Factor V leiden most common, pro-thrombotic inherited condition) Risk stratification: WELLS score (2+ = DVT likely) Ix: Bloods (FBC, U+E's, D-dimer, LFTs, Coag) Imaging (Doppler US, venogram, ct imaging) Management: Mainly with Anticoagulation (LMWH**)

Answer 16

Haematocrit = Proportion of RBC Classifications of polycythaemia: Relative vs True - RELATIVE when plasma volume depleted (e.g. dehydration or diuretics) - TRUE when excess RBC production (e.g. EPO, Polycythaemia vera, androgen)

Answer 17

Who? Generally young Children Cause: Typically secondary to infection (Shiga toxin from Ecoli 0157, pneumococcal, HIV) or SLE/Drugs/Cancer Atypically a primary HUS due to complement dysregulation Presentation: Background of diarrhoea Triad: AKI + MAHA + Thombocytopaenia Ix: FBC (Macrocytic anaemia), Stool sample, fragmented blood function Management: 1st line SUPPORTIVE (fluids, blood transfusion, dialysis). 2nd line Plasma exchange if severe HUS not associated with diarrhoea

Answer 18

Definition: Neutrophil count of 0.5 x 109/L or lower. AND temperature >37.5 or <36 or s/s infection Timing Nadir (post chemo lowest level of white blood cells) is at 7-21days post chemo ``` Who? Highly myelosuppressive regimens used in lymphoma and leukaemia Risk factors • >65 yrs • Poor performance status • Previous Hx of neutropenic sepsis • Combined chemo-radiotherapy • Poor nutrition • Advanced disease • Co-morbidities • Active wounds and infections ``` Presentation: Fever +/- focal infective symptoms Management Immediate: Sepsis 6 (with Tazocin and Gent within 1 hour, cultures of swabs, lines, bloods) + chest x-ray Further: Continue broad spectrum Abx for 24hours awaiting microbiology. Remove lines in situ. If cause unknown, consider adding antifungal or CTCAP

Answer 19

1. Intrinsic pathway of the aPTT (activated partial thomboplastin time) using all the coag factors + Extrinsic pathway of the PT (prothrombin time) starting with TF using Factor VII 2. --> Produce Factor X 3. Factor X catalyses Prothrombin to Thrombin. 4. Thrombin catalyses fibrinogen (soluble) to fibrin (insoluble)

Answer 20

Elements: - aPTT - PT - Fibrinogen content

Answer 21

``` Hb: 130-180 (males), 115-160 (female) MCV: 78-98 WBC: 4-11 x10to9/L Platelets: 150-400 x10to9/L Neutrophils 2-7 ```

Answer 22

Indication: Those with high bleeding risk (Peri-operatively, haemodialysis, acute limb ischaemia) Route: IV (aPTT dependent) MoA: Targets Factor X and thrombin Duration: Reversible with short half-life Monitoring: aPTT every 6 hours until stable then daily Reversal: Stop UFH. If crises give protamine Risk: Bleeding, HIT (heparin induced thrombocytopaenia), osteoporosis

Answer 23

MoA: Oral Vit K antagonists (blocks production of coag factors in extrinsic pathway) Action onset: Delayed due to Vit K stores so give heparin during induction Uses: - DVT - PE - AF - Artificial heart valves - Cardioversion Monitoring: - INR using PT - Normal =1 - Target 2-3 Duration is indication dependent: - Below the knee DVT = 6 weeks - Proximal DVT/PE, temporary risk factor/ idiopathic = 3 months Reversal guidelines: 1. Always stop warfarin once INR about 4.5 2. If bleeding --> - Major = IV Vit K 5mg + Beriplex IV (i.e. Prothrombin Complex Concentrate, PCC) - Minor = VIt K 2mg IV/ORAL) 2. If not bleeding --> - INR >7 = give IV/ORAL Vit K 2mg. - INR 4.5-6.9 = High risk get 1mg Vit K IV or ORAL. Low risk get Warfarin reduced or dose witheld. 3. Always recheck INR within 24 hours. If not corrected consider other causes (DIC, coag factor def, Liver disease, Lupus inhibitor, inadequate replacement) Interactions: Metabolised by cytochrome P450 system. Also metabolised in this system: - Alcohol - Incurrent illness -Diet - Drugs (If INR increases think PPI, azithromycin, cranberry juice. If INR decreases think rifampicin or anti-epileptics) Complications - Haemorrhage - Teratogenic - Soft tissue necrosis at buttock or breast on administration - Cutaneous (Alopecia, itchy MP rash)

Answer 24

MoA: factor Xa and thrombin inhibitor Main Uses of DOACs - VTE prophylaxis - VTE treatment - Atrial fibrillation - Acute coronary syndrome Advantages over warfarin - Rapid onset and offset - Fewer drug interactions - Fixed dosing - No routine monitoring ``` Disadvantages - Unsafe in advanced renal impairment - Not as effective for metallic heart valves - Bleeding Reversal agents pending ``` E.g. Rivaroxaban, Apixaban (if eGFR reduced)

Answer 25

Potentiates antithrombin which blocks thrombin and factor X

Answer 26

Delayed immune mediated reaction, occurring at day 5-10 of treatment. Is a prothrombotic condition

Answer 27

Type: Allogenic and Autologous Allogenic: Stem cells are harvested from the donor and infused to patient after they have undergone conditioning therapy Autologous: Peripheral blood stem cells harvested and undergo cryopreservation.Patient have conditioning therapy and stem cells are re-infused.

Answer 28

Donor eligibility: - Anyone anyone 17-66yrs - Every 12 weeks - DHC done before What happens? 1. Questionnaire on arrival 2. Consent 3. Anaemic test with finger prick (women <125. Men <135) 4. Blood taken, takes 5-15 mins and collected into blood bag (contains anticoagulant CPD). Testing the blood How: First 30ml of donated blood What is tested: - Matching (ABO, RhD, red cell phenotype) - Mandatory infections (HBV,HCV, HEV, HIV 1 and 2, Syphilis, HTLV I/II) - Discretionary infections (CMV, Malaria, Trypanosomiasis, West Nile Virus, Haemoglobin S, High titre anti-A +/- anti-B)

Answer 29

Blood components = RBC, plts, cryoprecipitate (fibrinogen), fresh frozen plasma Blood products = Albumin, Anti-D Ig, IV Ig, prothrombin complex Storage of blood component: Packed red cells - 35 day shelve life at 2-6 degrees Plts - 5-7 day shelve life at 20-24 degrees FFP - 36 months shelve life at -25 degrees Indications / Dose/ Compatibility of blood components: 1. Packed Red Blood Cells - Indications = Anaemia and blood loss (if symptomatic and Hb <70g/l) - Dose = Give "1 unit" and reassess. If major bleed order 4-6 units - Compatibility = Must be ABO and RhD matched 2. Plts - Indication = Platelet dysfunction or thrombocytopaenia - Dose = 1 unit - Compatibility = RhD essential, ABO not 3. FFP - Indication = Clotting factor deficiency - Dose = 4 units in 70kg adults - Compatibility = ABO match if possible, group AB is universal donor. Blood product use Anti-D Ig - Prevention of HDN in Rh-ve owmen Iv Ig - Immunodeficiency patients Coag factors - Reverse warfarin HAS - Replacement fluid in therapeutic plasma exchange

Answer 30

CLASSIFICATION Timing: - Acute (with <24 of the transfusion) caused by acute haemolytic reaction, allergy/anaphylaxis, bacterial infection, TACO, TRALI - Delayed (after 24 hours of transfusion) caused by delayed haemolytic reaction, viral infection, malaria, TA-GvHD, post-transfusion purpura Severity: Mild (itchy rash, low grade fever, slight breathlessness) - Response? Complete transfusion Moderate (significantly unwell, hypotensive, tachycardia, high fever - Response? Stop transfusion, treat patient and investigate Severe (collapse / shock) - Response? Emergency treatment required Fatal - Response? Immediately reported!

Answer 31

Immediate: - Local measures and 1g tranexamic acid - Red recels PRN Early - FFP every 1-2 red cells - INR / aPTT <1.5 After >5 units red cells - Give cryo if fibrinogen <1.5 - Make sure plts >50

Answer 32

1. ACUTE HAEMOLYTIC TRANSFUSION REACTIONS Cause: ABO incompatibility therefore destruction by IgM Signs: - Loin pain - Dark urine - Low bp - DIC Treatment 1. Immediately terminated transfusion 2. Fluid resus with saline INFORM LAB! 2. DELAYED HAEMOLYTIC TRANSFUSION REACTION Cause: Alloimmunisation due to IgG antibodies e.g. anti-D, anti-C, anti-K When? Days- weeks after transfusion

Answer 33

1. Stop the transfusion and call for help. 2. Check the right blood is being given to the right patient – if there has been a mix-up there might be another patient somewhere having the wrong blood too. a. It is also sensible to check that the unit has no leaks, smell or clumps – all of these might suggest contamination. 3. Is this a mild reaction and are there any signs of… Mild fever ⇒ Diagnosis is FEBRILE NON HAEMOLYTIC TRANSFUSION REACTION --> treat with paracetamol. Urticaria ⇒ Diagnosis is MILD ALLERGIC REACTION --> treat with antihistamines. 4. Is this a moderate or severe reaction with a drop in blood pressure or shock? Bleeding /dark urine⇒ Diagnosis is ACUTE HAEMOLOTIC TRANSFUSION REACTION DUE TO ABO INCOMPATIBILITY --> maintain IV access and transfer to ITU will need renal support. Swelling / wheeze ⇒ Diagnosis is ANAPHYLAXIS --> treat with adrenaline and antihistamines. 5. As well as collapse, is there a high fever of 39°C or has the temperature risen by 2°C or more? ⇒ Diagnosis is BACTERIAL CONTAMINATION --> treat with broad-spectrum antibiotics. 6. Is the overriding symptom one of breathlessness? In which case look for fluid overload, and if no fluid overload consider an immunological reaction. Raised CVP ⇒ Diagnosis is TACO --> treat with diuretics. Normal CVP ⇒ Diagnosis is TRALI --> treat with oxygen and respiratory support. 7.Once the person caring for the transfused patient has called for help – the first thing to do is to check that the right blood is being given to the right patient by doing a documentation check.

Answer 34

1. ALLERGIC REACTIONS What? Allergen in the donor plasma, for which the patient has a allergen-specific IgE Signs: - Urticarial crash - Pruritis - Mild wheeze Risk factors: - Other allergies - Atropy - Transfusing products containing plasma i.e. FFP, apheresis platelets Prophylaxis: If patients have recurrence reactions and require regular transfusions, give antihistamines 20-30 mins before transfusion. Treatment: Simple urticaria require stopping transfusion. Given antihistamine until symptoms resolve, the restart transfusion 2. FEBRILE REACTIONS (FNHTR) What? Fever >38 degrees or temperature rise of 1-1.5, with no effect on BP or pulse. Patient can feel chills/rigors Cause: Patient antibodies reaction to donor WBC (prevented by leucodepletion) OR cytokines released by donor WBC during storage (leucodepletion doesn't remove the cytokines) Risk factors: Transfusion of RBC or platelets, not plasma. Treatment: Paracetamol

Answer 35

1. ANAPHYLAXIS What? Severe life-threatening allergic reaction of sudden onset (within 15 mins)MoA: Allergic reaction with IgE antibody activated mast cells, therefore release of vasoactive substances Prevention? Transfuse where anaphylaxis can be treated 2. TRANSFUSION RELATED ACUTE LUNG INJURY (TRALI) What? Severe breathlessness and hypoxia after transfusion, within 6 hours Cause: Donor anti-WBC antibodies reacting with host WBC, which stick in lung capillaries and cause damage. (Typical donor: Female with children) Diagnosis: - Hypoxia - Fever - Hypotension - Bilateral pulmonary infiltrates on CXR Prevention: Male donors used to make FFT and cryoprecipitate, blood components from females (i.e. RBC and pooled platelets) contain v little plasma. Apheresis platelets donors from females must be screened of anti-WBC antibodies. 3. TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD (TACO) What? Form of pulmonary oedema precipitated by fluid overload from transfusion. Signs: Breathlessness, esp during transfusion. Management: Small diuretic dose. Prevention: Pre-transfusion risk assessment (assessed risk of TACO). Guides flow, dose and concurrent diuretic use Reporting: All TACO cases, no matter how minor.

Answer 36

1. TA-GvHD Prevention: Irradiation of blood product for the immunocompromised, in case filtration failed Mechanism: Engraftment of donor lymphocytes as patient is immunocompromised or HLA-similar Risk: Multi-organ failure and death 2. Viral Transfusion transmitted infection Prevention: - Donor health check (DHC) questionnaire - Viral antibody testing (HCV, HIV and HTLV1) - Antigen testing (HBV) Nucleic acid testing (HCV, HIV and HEV)

Answer 37

Parental administration via SC Inj OD MoA: Protentiates anti-thrombin Indications: - PE/ DVT - Acute coronary syndrome Thromboprophylaxis (2nd line in pregnancy women) Monitoring: NONE Reversal: Use protamine Risk: Not for eGFR <30. Risk of HIT and osteoporosis less than UFH

Answer 38

Cryoprecipitate contains factor VIII, fibrinogen, von Willebrand factor and factor XIII

Answer 39

Phenytoin Cytotoxics Chloramphenicol Sulphonamides e.g. sulfsalazine

Haematology Flashcards

(63 cards)