Medicine Flashcards
Why may patients with haematological malignancy present to ICU?
- Complications of acute presentation e.g. DIC in APML
- Neutropenia and sepsis
- Respiratory failure - infection, oedema
- TLS
- GvHD
- Complications of chemo and HSCT
- GI dysfunction
- AKI
Neutropenia
Neutrophils < 0.5 x 10^9/l
neutropenic sepsis < 0.5 + clinical infection or temp > 38
what empirical abx should be used for neutropenic sepsis
broad spectrum, anti-pseudomonas - taozcin
add aminoglycoside if gram negative suspected
Chemotherapy complications
cytotoxic abx - bleomycin (pulp fibrosis), doxorubicin (cardiomyopathy)
anti-metabolites - methotrexate (pulmonary fibrosis, liver)
alkylating agents - cyclophosphamide (pneumonitis`0
anti-microtubule agents - vincristine (peripheral neuropathy)
Complications of HSCT
early < 100 days
-infection
- haemorrhage
- acute GVHD
- aplastic anaemia / graft failure
- venocclusive disease - hepatic sinusoidal obstruction
late > 100 days
- chronic GVHD
- infections
- chronic pulmonary disease
GVHD
immune mediate disease following allogenic HCT - complex interaction between donor and recipient
enteritis, dermatitis, hepatitis
clinical / histological diagnosis
seattle staging
1-4
percentage skin rash
bilirubin
GI fluid loss ml/day
chronic gvhd more diverse and presents like other autoimmune disorders
treatment of acute
- high dose seteroids
- immunosuppressants
- TPN
typhilitis
neutropenic enterocolitis
GI complication of chemotherapy
Cellular origins of haematological malignancies
common myeloid progenitor
- CML
- AML
myeloblast
- AML
common lymphoid progenitor –> lymphoblast
- ALL
lymphoblast –> B / T / NK cell
- Lymphoma
- CLL
B cell –> plasma cell
- myeloma
Sepsis in haematological malignancy
- consider indwelling lines
- higher risk of opportunistic microbes
- higher risk of MDR organisms
- daily micro input
Causes of bleeding in critically unwell patients
reduced haemostasis
- coagulation factor deficiency - sepsis, DIC, major haemorrhage, vit k deficiency
- platelet dysfunction. deficiency - sepsis, DIC, extracorporeal circuits, major haemorrhage, BM failure
hyperfibrinolysis
- inherited - haemophilia
- cirrhoss
- truauma
secondary disruption of haemostasis
- hypothermia
- hypocalcaemia
- acidosis
- anticoagulants
inherited bleeding disorders
Haemophilia A - F VIII deficiency
Haemophilia B - F IX deficiency
- x-linked recesive
- severity determined by magnitude of factor deficiency
- spontaneous bleeding, haemoarhtrosis, GU bleeding, ICH
VwF disease
- commonest inherited bleeding disorder
- easy bruising
Clotting catastrophes
thrombotic storm
- underlying procoagulant state
- trigger to initiate clotting
- rapid development of clots
catastrophic thrombotic syndroms
- APLS
- TTP
- DIC
- HIT
- Covid 19
DIC
Systemic activation of clotting pathways
generation of fibrin clots leading to organ dysfunction
consumptive coagulapathy
may present with bleeding or clotting or both
ISTH diagnosis
- underlying cause associated with DIC
- platelets
- fibrinogen
- PT
- FDPs
Treatment of DIC
- stable non-bleeding patients - monitoring
- platelets < 20, planned intervention or bleeding then transfuse
- TXA contraindicated
inheritable thrombophilia
loss of function
- protein c deficiency
- protein s defieicney
- antithrombin deficiency
gain of function
- factor v leiden
- APLS
suspect in thrombosis < 40, family history
Sickle cell disease
point mutation chromosome 11 alteration in B chain
HbA –> HbS unstable, precipitates
acute crises -
- vaso-occlusive - acute chest syndrome, stroke, long bone ischaemia, AKI
sequestration
aplastic (parvovirus)
mx - analgesia, rehydration
transfusion if indicated
prevention of sickling - oxygenation, hydration, temperature, analgesia, venous stasis
top up / exchange transfusions (CVA, MODS)
transfusions - viral screening, specialised, extended antibody screening
IX FBC, blood film, sickledex, electrophoresis
Haemophagocytic lymphohistiocytosis
aberrant hyper inflammatory hyperferitinaemic immune réponse syndrome
associated with life threatening cytokine storm
familial HLH / secondary HLH
secondary may be triggered by infection (viral, bacterial) or malignancy. if triggered by autoimmune condition - macrophage activation syndrome (SLE, stills disease)
diagnostic criteria 5 of 8 HLH-2004 / HScore
- fever
- splenomegaly
- cytopenias 2+ cell lines
- ferritin > 500
- high triclygerides, low fibrinogen
- haemophagocytosis on BM biopsy
failure of negative feedback controlling inflammation. failure to clear antigens
steroids anakinra (IL-1 antagonist)
mortality 50% +
Heparin induced thrombocytopenia
prothrombotic syndrome after exogenous heparin adminsitration
UFH > LMWH
Type 1 - uncommon, mild thrombocytopenia, non-immune, benign. sepsis / burns. continue heparin
Type 2 - more common, significant thrombocytopenia, immune mediated, thrombosis, heparin cessation
PF4 - following platelet activation, released and binds cell surface, modulates immune response
Type 1 - heparin binds PF4, lower activation threshold, aggregation and mild thrombocytopenia
Type 2 - heparin displaces PF4 and forms complex which triggers immune response. IgG anti-PF4 binds to complexes. platelet activation and thrombosis
thrombocytopenia in ICU
- consumption - DIC, HIT
- Bone marrow suppression - infection, malignancy
- autoimmune - ITP
- thrombotic microangiopathies - TTP, HUS
- liver disease, splenomegaly
decreased production
- sepsis
- BM failure
- alcohol
Consumption
- DIC
- PE
- Trauma
Diltuonal
- fluid resuscitation / massive transfusion
destruction
- Immune - ITP, HIT, APLS
- Non-immune - DIC, intravascular devices
HIT diagnosis and management
4 Ts = pretest probability score
- Thrombocytopenia 50% but > 20
- Timing - day 5-10 or < 1
- Thrombosis - new, skin necrosis
- oTher cause - not present
intermediate / high risk
- stop heparin
- use alternative - argatroban (direct thrombin inhibitor), Xa inhibtior, fondaparinux
- multiplate platelet aggregometer
- antigen ELISA - IgG to PF4
- haematologist
Porphyria
Group of disorders caused by disruption in heam syntesis
enzyme deficiency in various stages of pathways lead to accumulation
precipitation of acute attack
- medications - cyp450
- fasting
- pregnancy
- alcohol
- acute physiological stress - infection
Acute
- AIP (porphobilinogen deaminase)
- variegate porphyria
Non-acute
- porphoryia cutanea tarda
porphyria pathophysiolgy
- haem supply multistage synthetic pathway
- enzyme activity changes lead to accumulation of substrate (porphyrins)
acute attacks when haem requirements increased
spectrum of clinical features (neurovisceral attacks) - CNS - psychiatric, seizures, altered mental state
- ANS - abdo pain, HTN, tachycardia, nausea, vomiting, urinary retention
- PNS - motor neuropathy, pain
diagnosis - random urine for urinary porphobilinogen (protect from light)
management - haem arginate
- resp weakness - support as indicated
- cvs instability - propanolol, etc
- seizures - Benzes
- psych - olanzepien
- hyponatreemia, malnutition
- precipitant
- advice from porphyria specialist
haem arginate - seizures, progressive neuropathy, hyponatraemia 3mg/kg. may clot lines
Thrombotic microangiopathies
group of diseases microvascular and macrovascular occlusion from intraluminal thrombus, alongside MAHA and thrombocytopenia
- TTP
- HUS
- others
TTP
Pentad
- MAHA, thrombocytopenia, AKI, CNS, fever
presentations usually neurological sequelae, MOD, bleeding
cause
- reduced activity of ADAMTS-13 enzyme
- cleaves VwF
- reduced cleaving -> large VwF multimers –> platelet aggregates (brain, hart, kidney) organ failure. haemolysis occurs as RBCs sheared by aggregates
situations
- primary ADAMTS-13 impaired e.g. genetic
- secondary - HIV, pregnancy, drugs (quinine, trimethoprim), autoimmune
Ix
- ADAMTS-13 assay
- FBC, film, reticulocytes, fragments
- U+E
- autoantibodies ANA, RF
- coagulation screen
Mx
- PLEX 1.5x plasma volume x 3 then 1/24hr
- FFP if delay
- methylprednisolone
- transfusion
- underlying cause
HUS
spectrum of TTP
MAHA, thrombocytopenia, AKI
Typical HUS - diarrhoea +ve shigella toxoid
Atypical HUS - no diarrhoea - pregnancy, infection s.pneumonia, drugs, malignancy, AI
typical = supportive mx
atypical = Plexiglas
presentation of transfusion reactions
acute < 24hr
delayed > 24hr
presentations
- mild - fever or pruritus only
- moderate - fever > 39 and or rash or other non-severe
- life threatening - resp distress, airway compromise, CVS compromise, bleeding
types of transfusion reaction
acute
- febrile non-haemolytic
- haemolytic
- allergic reaction
- TRALI
- TACO
- Bacterial contamination
chronic
- infection - HIV, HBV, HCV
- TA-GVHD
generic management of transfusion reaction
- recheck blood and patient compatibility
- inspect blood product
- stop transfusion, disconnect
- return products and labelling to laboratory
- report - MHRA
specific life threatening transfusion reaction management
anaphylaxis - per usual
TRALI
- ARDS like within 6hrs
- immune or non-immune
- supportive mx
TACO
- acute pulmonary oedema within 6 hrs
- furosemide and supportive mx
acute haemolytic reaction
- donor antigen and recipient antibodies - haemolysis. fever, pain riggers, urticaria, hypotension
- falling hb, elevated bile, LDH, Coombs
- supportive mx, RRT
Adrenocorticol disorders
hyperaldosteronism - hypertension, low K+
- conns syndrome - primary
- secondary - low CO state, cirrhosis
Cushings syndrome - hypertension, DM, low K+, altered body habitus
- ACTH dependent - cushings disease
- ACTH independent - adrenal tumour, exogenous steroid
Adrenocortical insufficiency
- primary - Addisons - autoimmune neoplastic, haemorrhage, drugs
- secondary - ACTH deficiency - hypopituitarism , prolonged steroid
- tertiary - hypothalamic - infarct
features of acute adrenocortical insufficiency
C - vasoplegia, hypotension, shock
D - altered consciousness, lethargy, fatigue
E - abdo pain vomiting
F - dehydration
chronic features - skin crease pigmentation, anorexia, associated AI disease e.g. T1DM
Blood results - hyponatraemia, hyperkalaemia, hypoglycaemia, uraemia
Investigations
- random cortisol + U+E, glucose, ACTH, FBC
- short synacthen test , imaging
Management
- hydrocortisone 200mg + 100mg QDS (will influence short synacthen test)
- fludrocortisone if using steroid with weak mineralocorticoid
- fluid
- management of hypoglycaemia
- underlying cause
Critical illness related corticosteroid insufficiency CIRCI
hypothalamic impairment leading to relative corticosteroid deficiency
- refractory hypotension
- delirium, coma
- nausea, vomiting
Steroid conversion
- Hydrocortisone 100mg
- Prednisolone 25mg
- methylprednisolone 20mg
- dexamethasone 3.75mg
steroid trials
Corticus - septic shock. no difference in mortality, significantly quicker reversal of shock
Adrenal - septic shock - hydrocortisone 200mg - significantly faster reversal of shock
Aprocchs - hydrocortisone + fludrocortisone in septic shock - lower mortality and faster shock resolution
Crash - TBI steroids bad
DEXA-ARDS - steroids good
Recovery - steroids good covid
Steroids harmful
= TBI, cardiac surgery, spinal injury, GBS, CAP
DKA
glucose > 11
ketones > 3
pH < 7.3
death from cerebral oedema, hyperkalaemia, ARDS, precipitants