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BIO3CBH Clinical Biochemistry And Haematology

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BIO3CBH Clinical Biochemistry And Haematology

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Course Code: BIO3CBH
University: La Trobe University

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Country: Australia

Questions:

1. From the details given for Patient A, identify the condition most compatible with the results observed. Justify your answer in context of the clinical and laboratory findings.
2. Provide a critical account of the benefits and limitations of factor assays 3. Based on the results, what common coagulation conditions can you exclude?

 
 

Answer:
Concerned patient for this test result is 25 year old female living in Liverpool. At the time of the test, the patient already had three miscarriages during a period of three year. At the same timeframe, she was suffering from hair loss, pain in feet and hand, and fatigue. She also had mouth ulcers in her palate. The same test were performed fifteen weeks earlier and there is no significant difference between the two tests. From the patient’s Full Blood Count (FBC), it can be seen that the patient had lower (110 g/L) than normal haemoglobin level. Lower haemoglobin level is a common anomaly for normal FBC test and it is generally indicative of iron deficiency or anaemia (Lopez et al. 2016). Along with that, patient also had low white blood cell (WBC) and platelets count which are 3.5 X 109/L and 95 X 109/L respectively. Low WBC count is indicative of neutropenia whereas low platelet count is indicative of thrombocytopenia. The patient was also assessed for Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP). Patient’s ESR is 29 mm/hr which is twice of the normal range and CRP value is 5.2 mg/L which is also higher than the normal range. ESR and CRP are the oldest biological marker to identify inflammation in human body (Ansar and Ghosh 2013). Thus, it can be said that the patient has inflammation. Additionally, the patient was assessed on various coagulation factor assays. Patient’s Prothrombin Time (PT), D Dimer, Fibrinogen, ADAMSTS13 and C3 (Complement) values were in normal range which are 12 seconds, 0.3 mg/L, 3.4 g/L,  75% and 1 g/L respectively. However, patient has slightly higher aPTT and Dilute Russel Viper Venom Time (DRVVT) value. Furthermore, patient has been detected positive for the test of Anti-Nuclear Antibodies (ANA), Anti-Phospholipid Antibodies (APLS) and Anti-Double Stranded DNA antibodies (ADSDNA). Positive ADSDNA test suggest a higher risk of auto immune disease Lupus, although 25 percent patient with lupus test negative for this test (Wichainun et al. 2013). Furthermore, patient has tested positive for the ANA test which is generally used by physician as a screening tool for lupus (Yu, Gershwin and Chang 2014). Almost every patient with active lupus test positive in this test. However, sometimes a small percentage of people with other autoimmune diseases also test positive for this test. Nevertheless, the patient has also tested positive for APLS which also confirms the diagnosis of lupus. This test also signifies higher risk of miscarriage and blood clots. Therefore, form the above discussion, it can be said that the patient has tested positive in screening test for lupus and also has other associated symptoms like miscarriage, fatigue, hair loss and joint pain. Along with that the patient has tested positive in APLS and ADSDNA. The patient’s FBC analysis, ESR and CRP results are also suggestive of this. Hence, to conclude, it can be said that patient has the most compatibility and chance for lupus autoimmune disease. 
Haemorrhage and thrombosis are plays huge role in high mortality rate of traumatic injuries, stroke and ischemic heart diseases. For this reason hemostatic agents and anithrombotics are essential to this treatment. However, traditional methods like PT/INR and aPTT are not developed enough to provide all the needed information to a medical practitioner to treat and diagnose their patients timely (Lancé 2015). These tests only provides the information about the starting time of clotting but not the maximum thrombin formation or hemostatic capacity of clot formation. Although, measurement of these data are technologically possible right now. Presently, the clot waveform analysis (CWA), thrombin generation test (TGT) and the viscoelastic tests (TEG/ROTEM) are gaining momentum as global clotting test. Viscoelastic tests are particularly effective against haemorrhage whereas thrombin generation is very much useful against arterial and venous thrombosis (Snegovskikh et al. 2018). These techniques are in the threshold of widespread clinical use. Although, further research and evidence is needed to validate this new techniques properly. At present, there are only 2 semi-automated thromboelastometry devices are commercially available. These are i) ROTEM-analyzer, TEM international, Muenchen, Germany and ii) TEG-analyzer, Haemonetcis Corp., Braintree, MA, United States (De Pietri et al. 2018). 
Based on the patient’s analysis and assessment results, I will exclude one of the Anti-Phospholipid Antibodies (APLS) and Anti-Double Stranded DNA antibodies (ADSDNA) factor assays. Both factor assays are to determine autoimmune diseases and neither techniques is able to screen a disease alone (Perricone 2015). Thus, in my opinion, it is redundant to use both of them together while using Anti-nuclear Antibody (ANA) factor assays.  Additionally, I will also assess only activated Partial Thromboplastin Time (aPTT) test and not Mixing Study (50:50) aPTT test. It might be relevant and useful to perform Mixing Study (50:50) aPTT test if we are only using activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT). Hence, with regards to this case study, we can also exclude the Mixing Study (50:50) aPTT test. 
Patient for this case study is a female of 14 year old who is living in Liverpool. She visited the General Practitioner (GP) because she was off-colour for few weeks. Her symptoms include mild fever, muscle aches, fatigue and sore throat. After the inspection, her GP reported that she had swelling in both sides of her neck and her GP confirms the presence of lymphadenopathy. She was advised to undertake other diagnostic tests which includes Full Blood Count (FBC), Liver Function Tests (LFT) and Prothrombin time (PT). From the data FBC results, it can be seen that patient has a lower haemoglobin level (100 g/L) than normal range which is indicative of iron deficiency or mild anaemia. The patients White Blood cell Count (WBC) and platelets were within normal range which are 8.0 X 109/L and 325 X 109/L. Interestingly, lymphocytes count of the patient is more than 50 percent of total white cell count which is 5.1 X 109/L. The patient’s other testing parameters (Mean Cell Volume, Mean Corpuscular Haemoglobin, Prothrombin Time, activated Partial Thromboplastin Time, D Dimer, and Fibrinogen) are all within respective normal range. The patient has inflammation in her system which is indicated by the higher than normal Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) values. Furthermore, the patient has higher than normal alkaline phosphatase in her blood level which is 180 IU/L. This indicates that patient has problem with her liver or gallbladder like jaundice or hepatitis (Sharma, Pal and Prasad 2014). This assumption is further strengthen by the fact that patient’s aspartate aminotransferase level in blood is also higher than normal (Gonzalez et al. 2015) and the value is 55 IU/L. Patient was also undergone to the Paul Bunnell antibody test and was tested positive in this test. This test is commonly performed to detect the presence of infectious mononucleosis which mainly occurred in adolescence and among young adults (Mule 2018). Patient also have elevated number of lymphocytes which indicates the possibility of mononucleosis (Chew 2015). Patient’s alkaline phosphatase and aspartate aminotransferase suggests that patients have liver dysfunction. Studies have suggested that liver abnormalities like jaundice or hepatitis are sometimes associated with mononucleosis (Moniri et al. 2017). Apart from that, patient’s GP has detected that she has lymphadenopathy along with mild fever, muscle aches, fatigue and sore throat. All this symptoms are indicative of the presence of infectious mononucleosis or glandular fever. Hence, from above discussion and patient’s assessment data it can be inferred that the patient is most likely suffering from infectious mononucleosis or glandular fever. 
The blood film that will be discussed here is from Patient B. The blood film were stained by Romanowski strain and were viewed under 400 time magnification. At a first glance, the blood film appears to be normal. Erythrocytes, white blood cells and platelets are present in normal ratio. Although, there are some abnormalities, deformities and irregularities can be observed. Firstly, at the top centre of the blood film a lymphocyte can be seen with a single large nucleus. Another, white blood cell can be partially seen in the left side which might be a lymphocyte or monocyte. The top centre lymphocyte has an abnormal outer cell structure which is indicative of viral infection. The RBC’s are slightly smaller in size than normal. Interestingly, the RBC in this blood film have a large zone of central pallor. This condition suggests the condition of microcytic anaemia (smaller than normal size) and hypochromic (lower haemoglobin in every RBC) (Hennek et al. 2016). Additionally, the RBC’s in this film are varying in size and shape. This evidence indicative of the condition poikilocytosis (varying RBC shape) and anisocytosis (varying RBC size) (Ceciliani 2017). 
Determined results of PT and aPTT tests for the patient A, B, C, D, and E are mentioned below:
Table 1: PT and aPTT results for the patient A, B, C, D, and E 

 

Patient A (Control)

Patient B

Patient C

Patient D

Patient E

PT (Sec)

19±2

14±0

17.5±0.5

14±2

17.5±0.5

aPTT (Sec)

17

15

16

16

18

References
Ansar, W. and Ghosh, S., 2013. C-reactive protein and the biology of disease. Immunologic research, 56(1), pp.131-142.
Ceciliani, F., 2017. Anaemia and oxidative stress in calves: an ironclad problem?. Veterinary Record, 181(10), pp.263-264.
Chew, J.M. and Cader, R.R., 2015. Presentations of Infectious Mononucleosis in Young Adults. Proceedings of UCLA Healthcare, 19.
De Pietri, L., Montalti, R., Nicolini, D., Troisi, R.I., Moccheggiani, F. and Vivarelli, M., 2018. Perioperative thromboprophylaxis in liver transplant patients. World journal of gastroenterology, 24(27), p.2931.
Gonzalez, F.A., Van den Eynde, E., Perez?Hoyos, S., Navarro, J., Curran, A., Burgos, J., Falcó, V., Ocaña, I., Ribera, E. and Crespo, M., 2015. Liver stiffness and aspartate aminotransferase levels predict the risk for liver fibrosis progression in hepatitis C virus/HIV?coinfected patients. HIV medicine, 16(4), pp.211-218.
Hennek, J.W., Kumar, A.A., Wiltschko, A.B., Patton, M.R., Lee, S.Y.R., Brugnara, C., Adams, R.P. and Whitesides, G.M., 2016. Diagnosis of iron deficiency anemia using density-based fractionation of red blood cells. Lab on a Chip, 16(20), pp.3929-3939.
Lancé, M.D., 2015. A general review of major global coagulation assays: thrombelastography, thrombin generation test and clot waveform analysis. Thrombosis journal, 13(1), p.1.
Lopez, A., Cacoub, P., Macdougall, I.C. and Peyrin-Biroulet, L., 2016. Iron deficiency anaemia. The Lancet, 387(10021), pp.907-916.
Moniri, A., Tabarsi, P., Marjani, M. and Doosti, Z., 2017. Acute Epstein-Barr virus hepatitis without mononucleosis syndrome: a case report. Gastroenterology and Hepatology from bed to bench, 10(2), p.147.
Mule, P., 2018. Heterophile Antibody Positive Infectious Mononucleosis by Epstein Barr Virus (EBV)-A Short Review. Acta Scientific Microbiology, 1, pp.44-49.
Perricone, C., Ceccarelli, F., Massaro, L., Alessandri, C., Spinelli, F.R., Marocchi, E., Miranda, F., Truglia, S., Valesini, G. and Conti, F., 2015. AB0555 Systemic Lupus Erythematosus with or Without Anti-Dsdna Antibodies: not so Different. Annals of the Rheumatic Diseases, 74, p.1085.
Sharma, U., Pal, D. and Prasad, R., 2014. Alkaline phosphatase: an overview. Indian Journal of Clinical Biochemistry, 29(3), pp.269-278.
Snegovskikh, D., Souza, D., Walton, Z., Dai, F., Rachler, R., Garay, A., Snegovskikh, V.V., Braveman, F.R. and Norwitz, E.R., 2018. Point-of-care viscoelastic testing improves the outcome of pregnancies complicated by severe postpartum hemorrhage. Journal of clinical anesthesia, 44, pp.50-56.
Wichainun, R., Kasitanon, N., Wangkaew, S., Hongsongkiat, S., Sukitawut, W. and Louthrenoo, W., 2013. Sensitivity and specificity of ANA and anti-dsDNA in the diagnosis of systemic lupus erythematosus: a comparison using control sera obtained from healthy individuals and patients with multiple medical problems. Asian Pacific journal of allergy and immunology, 31(4), p.292.
Yu, C., Gershwin, M.E. and Chang, C., 2014. Diagnostic criteria for systemic lupus erythematosus: a critical review. Journal of autoimmunity, 48, pp.10-13.

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