Haem/Onc Flashcards
LMWH has the greatest inhibitory effect on which coagulation factor of the coaguation cascade
Inhibits Factor Xa
(Ativates Antithrombin III which forms a complex that inhibits Factor Xa)
Mechanism of action of unfractioned heparin
Forms a Complex to inhibit thrombin, Factors IXa, Xa, XIa and XIIa
Adverse effect of heparin - LMWH/Unfractioned
1) Bleeding
2) Thrombocytopaenia - HIT (>UFH)
3) Osteoporosis (>UFH)
4) Hyperkalaemia (Inhibits aldoesterone section
How do you monitor Unfraction Heparin function
APTT
What is Myelofibrosis
Myeloproliferative disorder
What is the pathophysiology of Myelofibrosis
1) Genetic cause with mutations (most commonly JAK2 V617F) in JAK2, MPL genes
2) Results in Megakaryocyte proliferation and resultant secretion of Platelet derived Growth factor
3) Bone marrow fibrosis due to increased collaged despoition within the bone marriw
4) Resultant Extramedullary Haemtopoesis
Symptoms of Myelofibrosis
1) Most common - Lethargy (Secondary to anaemia)
2) Weight loss and night sweats
Signs of Myelofibrosis
1) Massive splenomegally
Investigations to Dx Myelofibrosis
1) Blood film - Tear drop like Poikilocytes
2) Bloods - Anaemia, Rasied LDH and Raised Urate (Increased Cell turnover)
3) Bone marrow testing - Dry tap requiring trephine biopsy
4) Genetic classification
Rx of Myelofibrosis
1) Supportive - Including regular transfusions for anaemia
2) DMARD - JAK2 - Monoclonal Abx (Ruxolitinib)
3) Allogenic stem cell transfer for advanced disease in younger aptients
Causes of Piokilocytes
Seen due to extramedullary haemtopeisis:
- mYELOFIBROSIS
- Thalassemias
- Some lEukaemias
What is the pathophysiology of Heparin induced thrombocytopaenia
Unfractioned Heparin forms a complex with Platelet factor 4 (PF4)
This activates platelets and hence forms a pro-thrombotic state
How to manage HIT
Stop all heparins and switch to a direct Thrombin Inhibitor
- Dabigatran - Used in AF to prevent stroke
- Argobatran - requires APTT monitoring
- Bivalirudin - PCI
How to diagnose Heparing induced thrombocytopaenia
ELISA-SPOT Assay to look for Hperain-PF4 complexes or serotonin release assay
NB - Drop in platelets of >15% after starting Heparin is not diagnostic
How many days after heprain starting would you expect HIT
5-10 days if heparin naive or quicker if previous exposure to heparin (UFH»_space;> LMWH)
CLL Gene mutation
BCR-ABL - t(9:22) - Philadelphia chromosome seen in >95% of patients with CLL
- Encodes for a RTK
Genetic mutation in Burkitt’s Lymphoma
MYC oncoogene t(8:14)
Genetic mutation in Acute promyelocytic luekaemia
RAR-Alpha and PML genes
t(15:17)
Genetic mutation in follicular lmphoma
t(14:18) - BCL-2 trancription is increased
Genetic mutation in Mantle cell lymphoma
t(11:14) - Deregulation of cyclin D1
What is the Tumour antibody marker for ovarian cancer
CA 125
What is the Tumour antibody marker for Peritoneal cancer
CA 125
What is the Tumour antibody marker for Pancreatic cancer
CA19-9
What is the Tumour antibody marker for BREAST cancer
CA 15 -3
What is the Tumour Antigen marker for Prostate cancer
PSA
What is the Tumour Antigen marker for HCC cancer
AFP
What is the Tumour Antigen marker for Colorectal cancer
CEA (Carcino embryonic antigen)
What is the tumour marker for SCLC
Bombesin
What is the tumour marker for melanoma
S-100
