2. Bleeding Flashcards

Question

At what platelet level should you give platelets in active bleeding

Answer 1

Offer platelet transfusions to patients with a platelet count of <30 x 10 9 with clinically significant bleeding (World Health organisation bleeding grade 2- e.g. haematemesis, melaena, prolonged epistaxis) Platelet thresholds for transfusion are higher (maximum < 100 x 10 9) for patients with severe bleeding (World Health organisation bleeding grades 3&4), or bleeding at critical sites, such as the CNS. It should be noted that platelet transfusions have the highest risk of bacterial contamination compared to other types of blood product.

Answer 2

Platelet transfusion for thrombocytopenia before surgery/ an invasive procedure. Aim for plt levels of: > 50×109/L for most patients 50-75×109/L if high risk of bleeding >100×109/L if surgery at critical site

Answer 3

A threshold of 10 x 109 except where platelet transfusion is contradindicated or there are alternative treatments for their condition For example, do not perform platelet transfusion for any of the following conditions: Chronic bone marrow failure Autoimmune thrombocytopenia Heparin-induced thrombocytopenia, or Thrombotic thrombocytopenic purpura.

Answer 4

Immune (or idiopathic) thrombocytopenic purpura (ITP) is an immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex. It is an example of a type II hypersensitivity reaction.

Answer 5

usually children bruising petechial or purpuric rash bleeding is less common and typically presents as epistaxis or gingival bleeding

Answer 6

full blood count should demonstrate an isolated thrombocytopenia blood film bone marrow examinations is only required if there are atypical features e.g. lymph node enlargement/splenomegaly, high/low white cells failure to resolve/respond to treatment

Answer 7

usually, no treatment is required ITP resolves in around 80% of children with 6 months, with or without treatment advice to avoid activities that may result in trauma (e.g. team sports) other options may be indicated if the platelet count is very low (e.g. < 10 * 109/L) or there is significant bleeding. Options include: - oral/IV corticosteroid - IV immunoglobulins - platelet transfusions can be used in an emergency (e.g. active bleeding) but are only a temporary measure as they are soon destroyed by the circulating antibodies

Answer 8

Avoid contact sports Avoid intramuscular injections and procedures such as lumbar punctures Avoid NSAIDs, aspirin and blood thinning medications Advice on managing nosebleeds Seek help after any injury that may cause internal bleeding, for example car accidents or head injuries

Answer 9

Chronic ITP Anaemia Intracranial and subarachnoid haemorrhage Gastrointestinal bleeding

Answer 10

Thrombotic thrombocytopenic purpura (TTP) is a condition where tiny thrombi develop throughout the small vessels, using up platelets. As the problem is in the small vessels, it is described as a microangiopathy. microangiopathic haemolytic anaemia TTP is caused by a deficiency in ADAMTS13, a metalloprotease that cleaves von Willebrand factor multimers. This leads to the accumulation of ultra-large von Willebrand factor multimers, which promote platelet aggregation and thrombus formation. This may be inherited or acquired (Autoimmune disease, where antibodies are created against the protein (acquired)

Answer 11

Microangiopathic haemolytic anaemia Fever Disturbed neurological function (Tissue ischaemia and end-organ damage) Renal failure (Tissue ischaemia and end-organ damage) Thrombocytopenia

Answer 12

Plasma exchange Treatment is guided by a haematologist and may involve plasma exchange, steroids and rituximab.

Answer 13

This protein normally: Inactivates von Willebrand factor Reduces platelet adhesion to vessel walls Reduces clot formation

Answer 14

Heparin-induced thrombocytopenia (HIT) involves the development of antibodies against platelets in response to heparin (usually unfractionated heparin, but it can occur with low-molecular-weight heparin). Heparin-induced antibodies target a protein on platelets called platelet factor 4 (PF4).

Answer 15

The condition typically presents around 5-10 days after starting treatment with heparin. HIT antibodies bind to platelets and activate the clotting system, causing a hypercoagulable state and thrombosis (e.g., deep vein thrombosis). They also break down platelets and cause thrombocytopenia. Therefore, there is a counterintuitive situation where a patient is on heparin, has a low platelet count, and develops abnormal blood clots.

Answer 16

testing for HIT antibodies on a blood sample.

Answer 17

1. Stop heparin + using an alternative anticoagulant guided by a specialist (e.g., fondaparinux or argatroban).

Answer 18

triggered by a bacterial toxin called shiga toxin --> thrombosis within small blood vessels throughout the body (THROMBOCYTOPENIA) blood clots (thrombi) partially obstructing the small blood vessels --> destruction of red blood cells as they travel through the circulation through the circulation (HAEMOLYTIC ANAEMIA) red blood cells block the kidneys --> (ACUTE KIDNEY INJURY)

Answer 19

The use of antibiotics and anti-motility medications such as loperamide to treat gastroenteritis caused by these pathogens increases the risk of developing HUS.

Answer 20

brief gastroenteritis, often with bloody diarrhoea The symptoms of haemolytic uraemia syndrome typically start around 5 days after the onset of the diarrhoea. Reduced urine output Haematuria or dark brown urine Abdominal pain Lethargy and irritability Confusion Oedema Hypertension Bruising

Answer 21

Urgent referral to the paediatric renal unit for renal dialysis if required Antihypertensives if required Careful maintenance of fluid balance Blood transfusions if required 70 to 80% of patients make a full recovery.

Answer 22

Sodium valproate Methotrexate

Answer 23

Drinking alcoholic beverages regularly and in higher than recommended quantity has been shown to cause bone marrow suppression, defective platelet formation, a decrease the lifespan of a platelet leading to premature removal from the body, and impaired platelet function.

Answer 24

acute lymphoblastic leukemia

Answer 25

acute lymphoblastic leukemia

Answer 26

Leukaemia is a form of cancer of the cells in the bone marrow. A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell. The excessive production of a single type of cell can lead to suppression of the other cell lines, causing underproduction of other cell types. This results in a pancytopenia, which is a combination of low: Red blood cells (anaemia), White blood cells (leukopenia) Platelets (thrombocytopenia)

Answer 27

An urgent full blood count

Answer 28

anaemia: lethargy/fatigue and pallor neutropaenia: frequent or severe infections thrombocytopenia: easy bruising, petechiae Hepatosplenomegaly: due to leukemic infiltration Fever: A persistent, recurrent or refractory fever that is most likely a constitutional symptom and may present alongside a history of night sweats, weight loss. Lymphadenopathy: a build-up of large numbers of cancerous cells which have travelled from the bone marrow Failure to thrive (children)

Answer 29

due to leukemic infiltration

Answer 30

a build-up of large numbers of cancerous cells which have travelled from the bone marrow

Answer 31

They recommend children or young people with petechiae or hepatosplenomegaly are sent for immediate specialist assessment.

Answer 32

- FBC - lactate - bone marrow biopsy - CT and PET scans - lymph node biopsy - genetic tests

Answer 33

- myeloid --> (megakaryocyte (--> thrombocytes), erythrocyte, mast cells, myeloblast ) then myeloblast --> basophil, neutrophil, eosinophil, monocyte (--> macrophage) - lymphoid --> natural killer cell and small lymphocyte. small lymphocyte --> T lymphocyte, B lymphocyte (--> plasma cell)

Answer 34

slow proliferation of a single type of well-differentiated lymphocyte, usually B-lymphocytes. It usually affects adults over 60 years of age. It is often asymptomatic but can present with infections, anaemia, bleeding and weight loss. It may cause warm autoimmune haemolytic anaemia.

Answer 35

Richter’s transformation refers to the rare transformation of CLL into high-grade B-cell lymphoma.

Answer 36

chronic - years of high WCC accelerated - blast cells push out other types - anaemia, thrombocytopenia, immunodeficiency blast phase - over 20% blasts in blood - severe symptoms and is often fatal

Answer 37

philedelphia chromosome This refers to an abnormal chromosome 22 caused by a reciprocal translocation (swap) of genetic material between a section of chromosome 9 and chromosome 22.

Answer 38

from middle age onwards

Answer 39

myeloprolifertaive disorder such as polycythaemia vera or myelofibrosis

Answer 40

A blood film and bone marrow biopsy will show a high proportion of blast cells. Auer rods in the cytoplasm of blast cells are a characteristic finding in AML.

Answer 41

Leukaemia is mainly treated with chemotherapy and targeted therapies, depending on the type and individual features. Examples of targleted therapies include (mainly used in CLL): Tyrosine kinase inhibitors (e.g., ibrutinib) Monoclonal antibodies (e.g., rituximab, which targets B-cells) Other treatments options include: Radiotherapy Bone marrow transplant Surgery

Answer 42

Failure to treat cancer Stunted growth and development in children Infections due to immunosuppression Neurotoxicity Infertility Secondary malignancy Cardiotoxicity (heart damage) Tumour lysis syndrome

Answer 43

Tumour lysis syndrome results from chemicals released when cells are destroyed by chemotherapy, resulting in: High uric acid High potassium (hyperkalaemia) High phosphate Low calcium (as a result of high phosphate) Uric acid can form crystals in the interstitial space and tubules of the kidneys, causing acute kidney injury. Hyperkalaemia can cause cardiac arrhythmias. The release of cytokines can cause systemic inflammation. Very good hydration and urine output before chemotherapy is required in patients at risk of tumour lysis syndrome. Allopurinol or rasburicase may be used to suppress the uric acid levels.

Answer 44

Precancerous disease of myeloid cells in bone marrow whereby the dysplastic cells may cause abnormal or inadequate blood cell rpoduction Badly fucntioning → anaemia, thrombocytopenia, leukopenia etc. Tries to compensate by increasing haematopoeisis Dysplasia has risk of progressing to acute myeloid leukemia

Answer 45

Myelodysplastic syndrome causes low levels of blood components that originate from the myeloid cell line: Anaemia (low haemoglobin) Neutropenia (low neutrophil count) Thrombocytopenia (low platelets)

Answer 46

older age and previous chemotherapy or radiotherapy.

Answer 47

Patients may be asymptomatic. It may be diagnosed after incidental findings on a full blood count. They may present with symptoms of: Anaemia (fatigue, pallor or shortness of breath) Neutropenia (frequent or severe infections) Thrombocytopenia (bleeding and purpura)

Answer 48

Full blood count will be abnormal. There may be blasts on the blood film. Bone marrow biopsy is required to confirm the diagnosis.

Answer 49

Watchful waiting Supportive treatment (e.g., blood or platelet transfusions) Erythropoietin (stimulates red blood cell production) Granulocyte colony-stimulating factor (stimulates neutrophil production) Chemotherapy and targeted therapies (e.g., lenalidomide) Allogenic stem cell transplantation (risky but potentially curative)

Answer 50

Myeloma is a cancer of the plasma cells (type of B lymphocytes that produce antibodies). Cancer in a specific type of plasma cell results in large quantities of a single antibody being produced.

Answer 51

is where there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer.

Answer 52

B cells in bone marrow producing antibodies → genetic mutation causing one antibody to be produced uncontrollably (50% of the time this is IgG) Bone marrow infiltration → anaemia, neutropaenia, thrombocytopaenia Plasma cells releasing cytokines → increased osteoclast activity → myeloma bone disease → skull, spine, long bones affected → bone pain / pathological fractures → releasing lots of calcium from bones → hypercalcaemia Kidney failure is common in patients with a monoclonal gammopathy, most frequently due to hypercalcemia or myeloma cast nephropathy. Immunoglobulin crystallization is an uncommon phenomenon that also results in kidney injury hypercalcaemia can ppt kidney stones,

Answer 53

PC: anaemia PC: neutropenia PC: thrombocytopenia PC: pathological fractures PC: bone pain, particularly back pain PC: myeloma renal disease PC: hyperviscosity PC: kidney stones

Answer 54

FBC: anaemia Calcium and bone profile: hypercalcaemia U&Es : renal failure ESR Plasma viscosity If suggetsive --> then very urgent (within 48hrs) - protein electrophoresis - bence-jones urine test if +ve 2ww bone marrow biopsy and look at all results

Answer 55

The diagnostic criteria for multiple myeloma requires one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma. Major criteria Plasmacytoma (as demonstrated on evaluation of biopsy specimen) 30% plasma cells in a bone marrow sample Elevated levels of M protein in the blood or urine Minor criteria 10% to 30% plasma cells in a bone marrow sample. Minor elevations in the level of M protein in the blood or urine. Osteolytic lesions (as demonstrated on imaging studies). Low levels of antibodies (not produced by the cancer cells) in the blood.

Answer 56

involves the removal of a patient's own stem cells prior to chemotherapy, which are then replaced after chemotherapy

Answer 57

Allogenic hematopoietic cell transplantation is not commonly used in myeloma due to high rates of overall mortality and symptoms of graft-ve

Answer 58

A combination of drugs is used to treat myeloma - 'induction therapy targeted drugs (such as thalidomide, lenalidomide, bortezomib, daratumumab) chemotherapy (such as cyclophosphamide or melphalan) steroids (such as prednisolone or dexamethasone) The particular combination depends on whether a patient may be suitable for autologous hematopoietic cell transplantation or not. Autologous hematopoietic cell transplantation involves the removal of a patient's own stem cells prior to chemotherapy, which are then replaced after chemotherapy prolong both event-free and overall survival when compared with non-transplant strategies typically it is younger, healthier patients who are suitable for stem cell transplantation and rigorous chemotherapy regimes.

Answer 59

pain: treat with analgesia (using the WHO analgesic ladder) pathological fracture: zoledronic acid is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly. infection patients receive annual influenza vaccinations they may also receive Immunoglobulin replacement therapy. venous thromboembolism prophylaxis fatigue treat all possible underlying causes if symptoms persist consider an erythropoietin analogue.

Answer 60

Sepsis and trauma lead to a release of pro-inflammatory cytokines in a so-called systemic inflammatory response. In other conditions, the expression of certain pro-coagulant factors, such as tissue factor, is upregulated. → activate clotting cascade → micro clots → multi-organ failure due to tissue ischaemia. plus clotting factors used up --> bleeding eg petechiae

Answer 61

Infection and septic shock tend to cause a more prothrombotic form of DIC, which predominantly causes excess clot formation. Alternatively, DIC due to obstetric catastrophes or leukemia tends to cause depletion of fibrinogen leading to hemorrhage. Low fibrinogen is more common in predominantly fibrinolytic types of DIC (e.g., patients with acute promyelocytic leukemia or obstetric-related DIC). Sepsis increases fibrinogen levels, so sepsis-induced DIC may have elevated or normal levels of fibrinogen. Falling fibrinogen may suggest ongoing DIC with consumption of fibrinogen.

Answer 62

Stopping bleeding - Platelet transfusions should be considered if the patient is bleeding. The platelet count should be maintained >50 x 109/L in the presence of bleeding. - In bleeding patients with a prolonged PT and/or APTT, fresh frozen plasma can be considered. - If there is severely low fibrinogen then transfusions of cryoprecipitate or fibrinogen concentrate should be considered. Stopping clotting - If thrombosis is a prominent feature, then therapeutic doses of heparin should be considered. If there is co-existing high risk of bleeding, then unfractionated heparin can be used since this has a significantly shorter half-life and is more readily reversible than low molecular weight heparin. - In other patients who are non-bleeding, prophylactic doses of heparin are recommended to protect against VTE.

Answer 63

Liver failure impacts all three stages of hemostasis: primary hemostasis, coagulation, and fibrinolysis Thrombocytopenia - platelet sequestration due to congetsive splenomegaly as a result of portal HTN - bone marrow suppression by alcohol/foalte def - imapired hepatic synthesis of TPO Coagulation - reduced synthesis of clotting factors - also reduction in anticoagualtion factors : Natural anticoagulant protein levels fall progressively with increasing severity of liver disease.6 Antithrombin, protein C and protein S levels OVerall “rebalanced hemostasis” According to this model, the hemostatic alterations that occur result in a new balance within and between procoagulant, anticoagulant and fibrinolytic systems (Figure 2).7 Because of the relative deficiency of procoagulant and anticoagulant factors, the hemostatic balance is more precarious and may tip toward bleeding or thrombosis depending on provoking circumstantial risk factors.

Answer 64

Breast-fed babies are particularly at risk as breast milk is a poor source of vitamin K. Maternal use of antiepileptics also increases the risk

Answer 65

The condition is caused by a lack of vitamin C in the diet, which is essential for the production of collagen and other important functions in the body. Symptoms of scurvy can include fatigue, weakness, joint pain, and bleeding gums. In severe cases, patients may experience anaemia and skin lesions.

Answer 66

Stop warfarin Give intravenous vitamin K 5mg Prothrombin complex concentrate - if not available then FFP*

Answer 67

Stop warfarin Give intravenous vitamin K 1-3mg Repeat dose of vitamin K if INR still too high after 24 hours Restart warfarin when INR < 5.0

Answer 68

Stop warfarin Give vitamin K 1-5mg by mouth, using the intravenous preparation orally Repeat dose of vitamin K if INR still too high after 24 hours Restart when INR < 5.0

Answer 69

Stop warfarin Give intravenous vitamin K 1-3mg Restart when INR < 5.0

Answer 70

Withhold 1 or 2 doses of warfarin (2 days) Reduce subsequent maintenance dose