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Haematology Flashcards

1
Q

Anaemia PC and O/E

A

PC - asymptomatic, can be tired, SOB, chest pain and in high output cardiac failure if severe. Can potentiate angina and claudication

O/E - mucosal pallour, tachycardia
koilonychia - long standing iron deficiency
jaundice ?haemolysis
peripheral oedema or hyperdynamic circulation - HF

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2
Q

Lymphoid progenitors

A

B cells maturing in bone marrows, T cells or NK cells formed from T cell progenitors in the bone marrow

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3
Q

Reticulocytes

A

Young RBC should comprise <2% of the red cells. Gives a guide to erythroid activity in the BM
High in times of haemorrhage or haemolysis
Low = BM failure or haemtinic deficiency

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4
Q

Myeloid progenitors

A

Granulocyte-macrophage progenitor = differentiates to neutrophils, dendritic cells and eosinophils
Megokaryocyte progenitor = Platelets
Erythroblast = RBC

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5
Q

Inappropriate EPO production

A

RCC

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6
Q

Microcytic anaemia causes

A

MCV <80

Thalassemia, Iron deficiency, sideroblastic anaemia

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7
Q

Iron deficiency anaemia

A

Increased loss = menorrghia, GI loss - haemorrhage
Low intake = elderly with poor diet
Malabsorption = Crohns and coeliac

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8
Q

Iron absorption

A

Cells in duodenal crypt can sense the bodys iron requirements allowing transport of iron across the apical membrane of the mucosal cells in the SI. Here it will stay stored in ferritin to be lost when the mucosal cells are shed or absorped into the plasma.

Hepcidin is a polypeptide which regulates the iron transport out of the cells binding to ferroportin and causing its internalisation and destruction. Therefore in low iron states such as anaemia hepcidin will be downregulated, Iron is transported in the blood bound to transferrin

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9
Q

O/E iron deficient anameia

A

Kolinychia = spoon shaped nails
Angular stomatitis

Plummer-Vinson syndrome = dysphagia, glossitis, iron deficient anaemia and oesophageal webs

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10
Q

Iron deficient anaemia Hx

A

NSAIDs - ?GI bleed, dietary iron intake = meat/cereal
PR bleeding - IBD, haemorrhoids, CRC
Females = ask about periods and menorrhagia

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11
Q

Ivx Iron deficient anaemia

A

High total iron binding capacity
Low ferritin and transferrin saturations
Low MCV

On blood film = poikilocytosis = variation in shape

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12
Q

Mx iron deficient anaemia

A

Find the cause
Iron supplements - ferrous sulphate 200mg TDS take when fasting

SE = nausea, constipation

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13
Q

Macrocytic anaemia causes

A

MCV >96
Megaloblastic - B12 deficiency, folate deficiency
Normoblastic - hypothyroid, chronic alcohol, liver disease

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14
Q

Causes of all anaemia

A

Reduced production = haematinic deficiency = B12, folate, iron and pernicious anaemia. BM failure, CKD and anaemia of chronic disease

Haemolyis

i) Intrinsic = sickle cell, G6PD, hereditary spherocytosis
ii) Extrinsic = AI haemolytic anaemia, DIC, TTP, HUS, malaria

Blood loss = haemorrhage, menorrhagia, GI tract = CRC, PUD, HHT, varices

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15
Q

Megaloblastic microcytic anaemia

A

Presence of erythroblasts in BM with delayed nuclear maturation due to defective DNA synthesis. Large immature nuclei

On blood film = hypersegemented polymorphs with oval shaped.

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16
Q

B12

A

Absorbed from the gut by binding to intrinsic factor produced by parietal cells presents insidiously with peripheral neuropathy, fatigue, SOB. Is linked to NO abuse

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17
Q

Pernicious anaemia

A

AI atrophic gastritis which leads to destruction of gastric parietal cells hence reduced intrinsic factor production. This leads to B12 deficiency and a microcytic anaemia.

Seen in elderly . Linked to other AI conditions such as thyroid disease, addison and vitiligo. Increased risk of gastric cancer. Progressive insidious onset with parathesia of extremities

Inx - parietal cell Ab +ve 90% sensitive, intrinsic factor ab only present in 50% but are specific for the condition.

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18
Q

Folate deficiency

A

Found in green veg, nuts, liver absorbed in the proximal jejunum.

Poor intake due to diet, GI malabsorption
Drugs such as methotrexate, trimethoprim and phenytoin
Increased use = pregnancy

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19
Q

Subacute combined degeneration of the spina cord

A

Due to B12 deficient. PC with mixed UMN and LMN signs, spastic paresis, ataxia, +ve rombergs, brisk knee reflex and absent ankles. Lose vibration and proprioception early

Due to degeneration of the dorsal columns - pain and temperature are still intact.

Mx = hydroxocobalamin 1mg IM

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20
Q

Normoblastic macrocytic anaemia

A

Hypothyroidism, chronic alcohol, lover disease
Aplastic anemia, myeloma and myelodysplasia

Crucially = normal vit B12 and folate

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21
Q

Normocytic anaemia

A

CKD, anaemia of chronic disease, myeloma, haemolytic anaemia, BM infiltration or fibrosis

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22
Q

Myeloma

A

Malignant disease of BM plasma cells leading to mass proliferation of monoclonal Ab. Often IgG or IgA

This leads to IL-6 production, inhibiting osteoblasts, therefore unopposed osteoclast activity leads to lytic bone lesions and high Ca2+

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23
Q

PC myeloma

A

Osteolytic bone lesions leading to # - spinal cord compression due to vertebral collapse
Hyperviscosity syndrome - headache, visual changes
Renal impairment due to build up of light chains and hypercalcemia - ATN
Recurrent infections due to neutropenia

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24
Q

Epidimology of myelomas

A

Increased risk in the elderly, afrocarribean and males

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25
Q

Inx myeloma

A

diagnosis = serum free light chains or urine electrophoresis, biopsy >10% clonal plasma cells
Normocytic anaemia
high Ca2+ , low PTH, U+E derangement, increased total protein
BM infiltration may = pancytopenia

CXR = lytic lesions - peppepot skull, vertebral collapse

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26
Q

Mx myeloma

A

Prevent complications i.e. bisphosphantes for hypercalcamiea, plasmapheresis for hyperviscosity.
Epo for anaemia, good hydration
Mx of pathological #

Chemo = lenalidomide + steroids. Then BMT

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27
Q

Polycythemia

A

> 55% Hb

Causes =
1 - polycythemia vera
2 - hypoxia = epo increase - athletes, altitude, smokers, chronic lung disease
inappropriate epo - RCC, HCC, steriods - androgens
relative - stress, dehydration

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28
Q

Thrombocytosis

A

Platelets >450
1 = myeloproliferative disorder
2 = reactive - Infection, inflammation, surgery, IBD, RA

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29
Q

Myeloproliferative neoplasms

A

Clonal stem cell disorders characterised by the uncontrolled proliferation of one of the erythroid, myeloid or megakaryocyte lines

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30
Q

Polycythemia vera

A

Excessive proliferation of erythroid, myeloid and megakaryocytes. 95% of suffers have a JAK2 mutation which allows proliferation without epo stimulation

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31
Q

JAK2

A

Cytoplasmic tyrosine kinase that transduces signals from epo. Its discovery allows easy diagnosis and a target for treatment

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32
Q

PC polycythmia vera

A

Insidious usually pt >60y/o with tiredness, headache and visual disturbance
Hyper viscosity syndorme = headaches, visual disturbance and tinnitus - increased VTE risk
Puritis post warm water exposure
Erythromelagia - burning pain in hands and feet combined with a reddish/blue discolouration of the skin
Gout

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33
Q

Complications of PV

A

Huge increase in VTE risk = stroke, DVT, MI,PE
Gout due to increased cell turnover
PUD due to increased histamine levels
Splenomegaly - hypersplenism (Not seen in 2ndary)

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34
Q

Inv PV

A

JAK2 +ve 95%
high RBC, WCC, plts, high Hb
low EPO
Biopsy = hypercellularity, with prominent myeloid and erythroid proliferation

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35
Q

Mx PV

A

Aspirin 75mg OD, Venesection to keep PCV <0.45
Hydroxycarbamide used for poorly controlled disease

30% = myelofibrosis

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36
Q

Pseudopolycythemia

A

Due to low plasma volume
Acute = shock, burns, dehydration
Chronic = diuretics

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37
Q

Essential thrombocythemia

A

Rare condition = overproduction of platelets. Usually isolated thrombocytopenia with plts >600

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38
Q

PC ET

A

Incidental finding. May present with erythromelgia, with a thromboembolic event, warm of the extremities or bleeding (less common)

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39
Q

Inv and Mx ET

A

Platelets >450 with absence of a 2nardy cause. JAK2 mutation in 50%.

Mx - Platelets 400-1000 = aspirin 75mg OD
>1000 = hydroxycarbimide

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40
Q

Primary myelofibrosis

A

Clonal proliferation of stem cells and abnormal myeloid cells in the BM, spleen and the liver. It can develop late secondary to PV or ET

Fibrosis is due to hyperplasia of megakaryocytes which release fibroblast growth factor such as PDGF. This leads to replacement of the BM tissue with connective and fibrotic tissue. Gradually will lead to pancytopenia

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41
Q

PC myelofibrosis

A

Massive splenomegaly due to extramedullary haematopoeisis. Lethargy, weakness, wt loss and fever. Bruising and easy bleeding

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42
Q

Inv myelofibrosis

A

BM biopsy = dry tap due to fibrosis
50% JAK2 +ve, tear drop polkilocytes
Initially high WCC and platelets progression to pancytopenia

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43
Q

Mx myelofibrosis

A

No cure - 5yr survival

Ruxolitinib

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44
Q

BM failure

A

Pancytopenia = aneamia, neutropenia and thrombocytopenia

On biopsy - hypocellular = fibrois/aplastic
hypercellular = Invasion of marrow = cancer

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45
Q

Causes of pancytopenia

A

Increased destruction = severe sepsis, hypersplenism

Reduced production = BM failure
Aplastic anaemia, severe megaloblastic anaemia, drugs-chemo or radiotherapy, BM infiltration = leukaemia, lymphoma, myeloma or 2ndary mets.

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46
Q

PC pancytopenia

A

Anaemia - tiredness, SOB, angina, pale tachycardia, high output HF

Neutropenia - huge infection risk of bacterial infections leading to uncontrollable sepsis, fungal infections = intracerebral abcess, reactivation of shingles

Thrombocytopenia = bleeding from gums, nose, petichae, purpura. Increased risk of GI and cerebral haemorrhage.

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47
Q

Assessment pancytopenia

A

Check B12/folate, rule out medications - clozapine, phenytoin, chemotherapy
USS to check size of spleen
BM biopsy - hypo vs hypercellular

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48
Q

Definition of neutropenic sepsis

A

Neutrophils <1.0
Pyrexia >38 for 1hr or >38.3 once

Seen commonly in those on immunosuppressive therapy and with BM failure

Crucial to sent cultures and start broad spectrum Abx within 1hr. Hunt for the source

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49
Q

Aplastic anemia

A

Pancytopenia + hypocellular bone marrow. Due to a reduction of pluripotent stem cells and a fault in the remaining ones meaning they are unable to repopulate the BM.

Present 15-24 and >60y/o

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50
Q

Causes of aplastic anaemia

A

60% idiopathic possibly due to HBV/HCV, AI
35% drug induced = chemotherapy, benzene, gold, penicillinamine, phenytoin, carbamazepine, ionising radiation

5% inherited = Fanconi’s anaemia

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51
Q

PC and Inv aplastic anemia

A

Anaemia, bleeding and infection

Inv = pancytopenia, no reticulocytes, hypo cellular BM

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52
Q

Mx aplastic anaemia

A

Intensive chemotherapy. Supportive and prophylactic ABx
BM transplant -
Autologous stem cells from pt. Radiation destroys leukaemia/BM
Allogenic HLA matched donor

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53
Q

Chronic myeloid leukemia (CML)

A

14% of leukaemias. In the family of myeloproliferative disorders. Exclusively a disease of adults 40-60

Increased and unregulated growth of the myeloid cells in the BM. 97% have philadelphia chromosome

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54
Q

Philadelphia chromosome

A

9:22 cr reciprocal translocation.BCR gene from cr 22 fused with the ABL gene on cr 9

When translated has enhanced tyrosine kinase and phosphorylation activity compared to normal protein. This gives a cascade of proteins that increase cell division

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55
Q

PC CML

A

Asymptomatic for long periods of time
Wt loss, fever, night sweats, hyper viscosity syndrome
Hepatosplenomegaly - bruising and bleeding

O/E - pallour = anaemia, massive splenomegaly,
If in blast phase - lymphadenopathy, extra medullary tissue deposit

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56
Q

Invx CML

A

increased WCC, basophils
platelets low or normal, may = normocytic anaemia
BM = hypercellularity with FISH for 9:22 translocation

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57
Q

Mx CML

A

Chronic phase <5% myeloblasts
Accelerated 10-19% myeloblasts
Blast phase - AML >20% with large clustered on BM

Imatinib - tyrosine kinase inhibitor

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58
Q

Chronic lymphocytic leukaemia (CLL)

A

Most common leukaemia in the western world. >70y/o 2:1 male to female ratio. Due to the clonal expansion of small B cells and their accumulation in the BM

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59
Q

PC CLL

A

Painless lymphadenopathy, fever, recurrent infection due to function leukopenia, anaemia
Wt loss, night sweat and fever

Complications - BM failure, infections often EBV, HZV, Richter syndrome - CLL to large B cell lymphoma
AI haemolysis

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60
Q

Inv CLL

A

High WCC, lymphocytosis > 5x109
BM - hyper cellular mass lymphocyte infiltration
Blood film - smudge cells
Rai and binet staging

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61
Q

Mx CLL

A

1/3 don’t progress, 1/3 chronically progress, 1/3 actively progressing

Steroids, chlorambucil, rituxamab

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62
Q

Poor prognosis in leukaemia

A

age and males
slow remission/ rapid relapse
high blast count
extra medullary disease

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63
Q

Hyperviscosity syndrome PC

A

Headaches, retinopathy, bleeding membranes - gums and GI, thrombosis risk.

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64
Q

Causes of high viscosity

A

High WCC - leukaemia
High plasma proteins - sickle cell, myeloma

Any cause of polycythemia i.e. PV, ET, 2ndary hypoxia

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65
Q

Causes of splenomegaly

A

Cirrhosis/congestion
Haematological - lymphoma, leukaemia, myelofibrosis, Infections - EBV, mononucleosis, malaria, TB
AI - SLE, RA, sarcoidosis

66
Q

Myelodysplastic syndromes

A

Increasing bone marrow failure with abnormalities in either platelets, RBC or monocytes

PC = elderly with pancytopenia, progressive BM failure with anaemia, neutropenia or thrombocytopenia.
30% to progress to AML

Inv - ringed sideroblasts, hypercellular BM,

67
Q

Lymphoma

A

Malignancy of the lymphoid tissue, most commonly presents with lymphadenopathy. Common B symptoms are wt loss, night sweats and fever

68
Q

When to refer lymphadenopathy to a specialist

A

Lymph node >1cm for 6 weeks
Supraclavicular lymphadenopathy
Generalised lymphadenopathy

69
Q

Differential diagnosis of lymphadenopathy

A

Reactive viral or bacterial infection - cat scratch, EBV, mesenteric adenitis
Lymphoma often widespread and painless
HIV - Primary infection
AI = SLE, RA, Kawasakis, sarcoidosis, TB

70
Q

History for lymphoma

A

Duration? painless - lymphoma
Risk factors for HIV/TB
B symptoms - wt loss, fever, night sweat
Cat scratch - tender swollen lymph nodes near site of injury may persist for months

71
Q

Inv for lymphadenopathy

A

Monospot test for EBV, viral screen TB, HIV
Blood film
LDH - high levels linked to a high tumour burden
B2 microglobulin - seen in myeloma, lymphoma and amyloidosis
Excision biopsy is crucial !!

72
Q

Hodgkin lymphoma

A

Reed sternberg cell - Owls eye

Incidence peaks 20-29 and >60y/o, 2:1 M:F, 3x increased risk with EBV

73
Q

PC Hodgkin lymphoma

A

Painless, asymmetric rubbery lymphadenopathy - usually at axilla, cervical or inguinal nodes
B symptoms = wt loss, fever, night sweats
Pel ebstein fever - cyclical fevers increasing then decreasing over a 1-2 week period
Splenomegaly and pruritis

Symptoms due to mass effect = cough, SVC obstruction

74
Q

Inv Hodgkin lymphoma

A

LN excision biopsy = diagnostic Reed Sternberg cell , CD15/CD30 +ve. Only for those stage III, IV or with B symptoms

FBC, blood film, LFTs , LDH, CXR and CT abdo thorax pelvis for staging

PET imaging can be used with radio labelled glucose showing metabolically active tissues

75
Q

B symptoms

A

> 10% wt loss in 6 months, fever >38, drenching night sweats

76
Q

Ann Arbour Staging

A 
I = single lymph node involvement 
II = 2+ nodes on the same side of the diaphragm 
III = Lymph nodes both sides of the diaphragm + spleen 
IV = Spread beyond nodes to bones, liver
77
Q

Mx Hodgkin lymphoma

A

ABVD chemo

78
Q

Infiltrative BM failure

A

Haematological = Leukemia, myeloma, lymphoma

Non haematological = Metastatic breast, prostate, lung, renal and thryoid

79
Q

Acute leukaemia

A

Classified as a rapid increase of immature blood cell due to ineffective haemopoiesis due to tissue infiltration by leukaemic cells.

80
Q

Characteristics of a blast cell

A

Immature precursor of a myeloid or lymphoid cell. Larger than their normal counterparts with an immature nucleus. Highly suggestive of acute leukaemia or a chronic conditions transforming i.e. myeloproliferative disorders /CML blast crisis

81
Q

Acute lymphocytic leukaemia (ALL)

A

Common in children <5y/o

82
Q

Risks for ALL

A

Cancer syndromes - ATM, Li fraumeni, NF1, Bloom and Fanconi
Radiation and chemotherapy
Downs syndrome
Genetic susceptibility + AI conditions

83
Q

PC ALL

A

BM failure = pancytopenia - anaemia (SOB, fatigue, palpitations) , neutropenia (fever, sepsis), thrombocytopenia (gum bleeding, petichae)

Wt loss, fatigue and night sweats

Tissue infiltration

84
Q

Tissue infiltration ALL

A

Lymphadenopathy,
Testicular enlargement,
Thymus/mediastinal enlargement - SVC obstruction or SOB
CNS - cranial nerve palsies

85
Q

Invx ALL

A

TdT+ lymphoblasts, high WCC
low RBC, platelets,
BM biopsy >20% blasts - T/B cells
CSF analysis crucial to determine if CNS involvement

86
Q

Mx ALL

A

98% children in remission and 85%@ 5 years
85% adults and 55% @ 5 years

Chemo aims to induce remission, given intrathecally to cross BBB and kill CNS progenitors.

Give allopurinol and hydrate to reduce risk of tumour lysis syndrome.

87
Q

AML

A

Common in adults 65-70y/o. Neoplastic proliferation of myeloid progenitors high levels of monocytes and granulocytes

Can be 2ndary to MDS and CML

88
Q

Classification of AML

A 
M2 = granulocyte maturation
M3 = Promyelocytic high risk of DIC t15,17
M4 = Acute monocytic - Gum hypertrophy, skin deposits
M7 = Megakaryocytic high risk in Downs
89
Q

PC AML

A 
Pancytopenia due to BM failure
Tissue infiltration
 - gum hypertrophy
 - Violaceous skin deposits
 - Hepatosplenomegaly
 - DIC if M3
90
Q

Inv AML

A

high WCC, low plts and Hb

BM aspirate >20% blasts, auer rods = diagnostic of myeloperoxidase crystals

91
Q

Mx AML

A

ABVD - adrimycin, bleomycin, vincristine and dacarbazine

Acute SE - alopecia and myelosuppression
Delayed SE - peripheral neuropathy, infertility, bleomycin - 20% lung fibrosis, cardiac toxicity, increased risk of leukemia

92
Q

Non-hodgkin lymphoma

A

85% of lymphomas no reed sternberg cells on biopsy
- 80% B cell and 20% T cell

Incidence increases with age 55-70y/o. Superficial lymphadenopathy painless at multiple sites. Frequency of B symptoms - wt loss, fever and night sweats

High incidence of extra nodal symptoms - splenomegaly, CNS, GI tract

93
Q

T cell lymphomas

A

Enteropathy T cell lymphoma = increased risk in coeliac disease.
Adult T cell = Japanese / carribean people

94
Q

Low grade B cell NHL

A

Follicular, MALT, small cell lymphocytic and Waldenstomrs (lymphoplasmacytic). These are generally not curable, but relapse and remit

95
Q

Follicular lymphoma

A

2nd most common NHL (20% of lymphoma worldwide)
No cure present, low grade long history

PC painless lymphadenopathy late onset 50-60y/o. Can transform to diffuse B cell lymphoma

Mx - anti-CD20 rituximab

96
Q

MALT

A

Occurs in mucosa associated with lymphoid tissue often in the stomach and linked to chronic h.pylori infection

97
Q

High grade B cell NHL

A

Diffuse large B cell, Burkitts

98
Q

Diffuse large B cell

A

Most common adult lymphoma worldwide. Can evolve from CLL and follicular NHL. Aggressive but rapidly response to treatment

99
Q

PC diffuse large B cell lymphoma

A

Painless lymphadenopathy at one or several sites, can have bowel symptoms from compression or infiltration of GI tract.

Death occurs within months if no treatment

100
Q

Poor prognosis for diffuse large B cell

A 
age >60y/o
stage III, IV
LDH high
ECOG performance status 2+
More than 1 extra nodal site
101
Q

Burkitts lymphoma

A

Most rapidly proliferating lymphoma, most common in childhood, 3:1 M:F. t8,14

i) Endemic always EBV associated, occurs in africa corresponds to malaria distribution

ii) Sporadic 30% EBV linked
iii) AIDS related

102
Q

PC Burkitts

A

Rapidly growing jaw tumours, abdominal mass associated with bone marrow involvement, kidney and the testis

103
Q

Mx high grade lymphoma

A

RCHOP regime of chemotherapy. Beware tumour lysis syndrome!

104
Q

Tumour lysis syndrome

A

Complication of cancer treatment involving large volume susceptible cancers i.e. myeloma, lymphoma high grade and leukemia

105
Q

PC tumour lysis

A

high k+, urate and phosphate
low calcium - precipitates with the high phosphate levels

This can lead to AKI, uric acid nephropathy, arrthymias due to K+ and death

106
Q

Mx tumour lysis syndrome

A

IV fluids to hydrate, allopurinol or rasburicase

107
Q

Haemostasis

A

Complex process to stop bleeding following tissue injury

108
Q

Vessel wall

A

Lined by endothelium which under normal circumstances prevents platelet adhesion and thrombus formation. This is due to to synthesis of NO and prostacyclin that cause vasodilation and inhibit platelet aggregation. Heparin sulphate and thrombomodulin expression

109
Q

Tissue injury

A

Reflex vasoconstriction of blood vessel occurs to reduce blood flow to the area, serotonin and thromboxane released by platelets allow this. The injury to the vessel wall exposes collagen. Platelets adhere to the collagen with the help of vWF. Its releases a cascade of granules and ADP which allows platelets to bind to fibrinogen and aggregate together. This cycle of ADP and glycoprotein II allows perpetuation of the cycle forming the platelet plug. The presence of thrombin from the coagulation cascade leads to fibrin formation which is cross linked by factor XIII

110
Q

Amplify and potentiate coag cascade

A

Factors XII, XI, IX, VIII lead to the thrombin burst

111
Q

Extrinsic pathway

A

Tissue damage leads to endothelial cells releasing tissue factor (III) this activates factor VII. PT

112
Q

Assessing the extrinsic pathway

A

PT. Looks at just factor VII. Increased in liver failure, vit K deficiency, DIC and very rarely = factor VII deficiency

113
Q

Vit K dependent clotting factors

A

II, VII, IX, X

114
Q

Liver dependent clotting factors

A

I,II, V

115
Q

Common pathway

A

Factor X when activated converts prothrombin (II) to thrombin (IIa) this crucially converts fibrinogen to fibrin!. Factor XIII then crosslinks the fibrin

116
Q

Intrinsic Pathway

A

Activated by collagen exposure. XII, XI, IX and XII. Assessed by the APTT. Increased in vWD, haemophilia A/B, DIC, hepatic failure and with lupus anticoagulant.

117
Q

Bleeding History

A

Easy bruising to minimal trauma
Gum bleeding and epistaxis
Prolonged bleeding in surgery
FHx

118
Q

Haemophilia A

A

X-linked disorder seen in 1/5000 males - deficiency of factor VIII. 1/3rd of cases sporadic
Classified according to residual factor VIII levels.
- severe <1%, mild >5%

119
Q

PC haemophilia VIII

A

Haemoarthroses - bleeding into joint spaces causing chronic pain and deformity
Raised palpable haematomas
Haematuria and increased risk intracranial haemorrhage

120
Q

Invx and Mx haemophilia

A

Increased APTT - crucially this correct when mixed with normal plasma due to availability of clotting factors, if this doesn’t correct lupus anticoagulant

Mx - recombinate factor VIII IV injections
avoid aspirin, NSAIDs and heparin
mild disease = DDAVP stimulate vWF

121
Q

Haemophilia B

A

Deficiency in factor IX. Seen in 1/25000, X-linked

PC = old age after surgery, investigations shows increased APTT.

Mx = Factor IX concentrates

122
Q

vWF

A

Crucial to stabilise platelets binding to collagen at the site injury of the endothelium. Without out this platelets are unable to aggregate and form the platelet plug

123
Q

Von Willebrand disease

A

Commonest inherited bleeding disorder 1/1000.

  • Type 1 AD reduced levels of vWF
  • Type 2 AD qualitative abnormality
  • Type 3 AR - complete deficiency of vWF
124
Q

PC vWF

A

Type 1+2 = easy bruising and increased risk of bleeding
Type 3 = More severe bleeding after surgery, GI bleeds

Inv = increased APTT, low VIII and vWF

Mx - DDAVP stimulates vWF release from endothelial cells, platelet derived factor VIII with vWF

125
Q

Vit K deficiency

A

Will show as a raised PT and APTT as both intrinsic and extrinsic pathways use vit K dependent clotting factors.

Haemorraghic disease of the newborn due to short t1/2 of foetal RBC, low vit K stores and brusing that often occurs at delivery. 1mg IM vit K given at birth.

126
Q

Acquired disorders of haemostasis

A

DIC, liver disease (low TPO), renal disease (high urea reduces platelet efficacy), vit K deficiency, anticoagulants

127
Q

Disseminated intravascular coagulation (DIC)

A

Systemic activation of the coagulation cascade where balance of procoagulant and anticoagulant factors is overwhelmed by systemic procoagulant signal

Usually due to mass tissue factor release or inflammatory cytokines

Widespread generation of fibrin and deposition in blood vessels leading to thrombosis, tissue ischemia and multi organ failure. This leads to mass consumption of platelets and clotting factors, secondary activation of fibrinolysis leads to bleeding

128
Q

Causes of DIC

A 
Gram -ve sepsis
Trauma - burns, rhabdomyolysis, 
Major haemorrhage 
Malignancy - AML (M3)
Obstetric catastrophe - preeclampsia, PPH, placental abruption
129
Q

Inv DIC

A

high d-dimer, high PT, APTT
low platelets <50 and fibrinogen
Fragmented RBC on film = schisocytes

May have bleeding from venipuncture sites, mouth, nose. Widespread ecchymoses

130
Q

Mx DIC

A

Treat the underlying condition, FFP - clotting factors, cryoprecipitate - fibrinogen, platelets and transfusion

131
Q

Thrombocytopenia

A

Reduced production - BM failure, megaloblastic anaemia,
Increased consumption - Immune = ITP, CLL, SLE, virus
non immune = DIC, TTP, HUS
Hypersplenism

132
Q

Idiopathic thrombocytopenic purpura (ITP)

A

Immune destruction of platelets due to antibodies against platelet surface antigens leading to increased splenic sequestration and macrophage phagocytosis.

133
Q

ITP PC

A

spontaneous bleeding and petichae, bleeding from nostrils and gums, menorraghia. Normal on physical exam

134
Q

ITP adults vs children

A

Children - 2-6yrs acute bleeding with viral infection EBV/measles recently

Adults - Seen in women with other AI disorders such as SLE, thyroid disease. Can be linked to CLL or solid tumours

Mx = usually self-liming, steroids can be used

135
Q

Thrombotic thrombocytopenic purpura (TTP)

A

Rare disorder where extensive microscopic clotting leads to a profound thrombocytopenia. Deficiency in ADAMS’S-13 enzyme which is responsible for breakdown of large vWF leading to large thrombi

PC - florid purpura, fever, altered mental state, microangiopathic haemolytic anaemia leading to AKI,

high LDH,

Mx = plasmapheresis

136
Q

Thrombophilia

A

Inherited or acquired defects of haemostasis leading to a predisposition to venous or arterial thrombosis

137
Q

Thrombus

A

A solid mass formed in the circulation from the constituents of blood

Arterial - Occurs in association with atheroma which tends to form at areas of turbulent blood flow such as bifurcation of arteries. Platelets adhere to the damaged endothelium and aggregate in response to ADP. Plaque rupture may expose tissue factor leading to coagulation cascade and thrombus

Venous- Virchow triads of hypercoagulabilty, stasis and endothelial damage. Consists of mainly fibrin and RBC

138
Q

Predisposition to thrombosis

A

AF, ventricular assist device, metallic heart valve
Antiphospholipid
Cancer
Pregnancy
Nephrotic syndrome
Congenital - antithrombin III deficiency, factor V leiden
Trauma, surgery,

139
Q

Patient risk factors for thrombosis

A

Age, female, immobility, smoking, obesity
PMHx
COCP

140
Q

Roles of protein C and antithrombin III

A

Protein C when activated degrades factor V and VIII with the help of protein S. They dampen the response of the intrinsic pathway

Plasmin degrades fibrin

Antithrombin III adhesion to factor IX, X, XI, XII and thrombin (II). Increased activity by presence of heparin sulphate

141
Q

Factor leiden V

A

Point mutation leads to arginine being replaced by glutamine @ position 506. This leads to slowed inactivation of Va as protein C is unable to bind to APC and degrade it. Seen in 5% of population

Homozygous - 80x VTE risk
Heterozygous - 8x VTE risk

142
Q

Antithrombin III deficiency

A

AD approx 1/500 people. Low levels of antithrombin III lead to more circulating thrombin and increased clotting risk

Heterozygous - increased clotting risk
Homozygous not compatible with life

143
Q

Protein C/S deficiency

A

AD conditons linked with increased risk of VTE
Homozygous = neonatal purpura fulminant fatal unless immediate replacement

Heterozygous = Increases risk of thrombosis and warfarin induced skin necrosis

144
Q

Prothrombin gene mutation

A

Mutation in the 3’ untranslated region of the prothrombin gene associated with 3x increased risk of VTE

145
Q

Pre test wells and d-dimer

A

i) pre test <1 and d-dimer -ve = alternative diagnosis

ii) pre test >1 and d-dimer +ve = doppler USS
USS = +ve treat !

146
Q

D-dimer

A

Breakdown product released when fibrin is broken down by plasmin. Sign of clot breakdown -ve predictive value of 96%

147
Q

Warfarin

A

Inhibits vit K epoxide reductase preventing recycling of vit K which is crucial to produce clotting factors II, VII, IX and X

148
Q

LMWH

A

Tinzaparin, enoxaparin ,dalteparin. All act by binding to anti-thrombin III and increasing the inactivation of thrombin.

149
Q

DOAC’s

A

IIa inhibitors = dabigatran

Xa inhibitors = Rivoroxaban and apixaban

150
Q

Treatment DVT/PE

A

a) LMWH - tinzaparin 175units/day continue until INR = 2 for 2 x readings. Then titrate warfarin dose up
b) Rivaroxaban - loading dose of 15mg BD for 21 days then 20mg OD

151
Q

Warfarin therapeutic window

A

Narrow >1 = risk of ischemic stroke, >3 risk of bleeding

Target INR 2.5 AF, PE, DVT, cardioversion
Target INR 3.5 mechanical valve, recurrent VTE on warfarin

152
Q

Reversal of warfarin

A

Omit warfarin = 2-4days
Oral vit K = 24hrs
IV vit K = 4-6hrs
PCC = 10 minutes

If INR >8 no bleeding = stop warfarin, 5mg oral vit K
INR 5-8 = stop warfarin and investigate

153
Q

Reversal of warfarin in intracerebral bleed

A

To prevent haematoma expansion and allow surgery if needed
i) Significant bleed no haemodynamic compromise = IV vit K 2mg check INR 4-6hrs

ii) If life, limb sight threatening or surgery needed immediately vit K 5mg IV and PCC (beriplex) IV 30U/kg

154
Q

Haemochromatosis

A

AR disorder involving HFE gene on cry leading to increased iron absorption and its subsequent deposition throughout the body

PC - bronzed skin, DM, arthralgia, cirrhosis, cardiomyopathy. Onset later in females as menstruation is protective

Invx = high ferritin, transferrin sats > 98%

155
Q

Major haemorrhage protocol

A

FBC, group and save, clotting screen
FFP:RBC in 1:2 - Use 0-ve blood until G&S returns
- Crucial to pass blood through a warmer otherwise can precipitate hypothermia!

Communication with the lab is crucial replace when needed

i) low Hb = RBC
ii) APTT >1.5 = FFP 20ml/kg
iii) Fibrinogen <1.5g/L = cryoprecipitate
iv) Platelets <50 = platelets

If trauma and <3hrs since injury give 1g bolus of transexmic acid followed by 1g IV over 8hrs

156
Q

Hereditary spherocytosis

A

AD abnormality of erythrocytes leading to malformed sphere shaped RBC due to membrane protein dysfunction . They have an increased risk of rupture = haemolytic anaemia

PC = splenomegaly due to abnormal RBC getting trapped leading to macrophage recruitment and phagocytosis , pigmented gallstones and anemias 
Inv = high MCV and reticulocyte count

Mx = splenomegaly after 5 y/o due to risk from encapsulated organisms

157
Q

Splenomegaly causes

A

Haem - hereditary spherocytosis, leukaemia, lymphoma, myeloproliferative

Portal HTN - cirrhosis, Budd-chairi
Connective tissue - RA, SLE, Sjogrens
Infiltrative - sarcoidosis, amyloidosis
Infective - EBV, CMV, HIV, TB, malaria

158
Q

Splenomectomy

A

May be indicated trauma, rupture (EBV), AIHA, ITP, hereditary spherocytosis and hypersplenism

SE = LLL atelectasis, susceptibility to capsulated pathogens Hib, pneumococcus, meningococcus.
Therfore vaccines, life long Abx

159
Q

Acute infection FBC?

A

High WCC, high platelets - crucial to check after resolution no evidence of myeloproliferative disorder

160
Q

Acquired haemophilia

A

Autoimmune usually antibodies to factor 8 or factor 9
Elderly patients with elevated APTT

Do 50:50 mix – no correction
About 50% - occult malignancy
Tx: steroids, immunosuppression e.g. rituximab

CSIM (12 decks)

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