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									            Omniscience
 Case 1
           Dr. Vivienne Ellis
           Department of Clinical Chemistry, SEALS – Kogarah Campus, New South Wales
           e-mail: Vivienne.Ellis@sesiahs.health.nsw.gov.au



            Case History
            A 34-year-old woman was referred to the renal clinic       Questions
            for investigation of labile hypertension. A diagnosis of   1.    On the basis of the history and results listed
            essential hypertension had been made 7 years previously          above what conditions would you include in your
            when the elevated blood pressure was first detected.             differential diagnosis?
            Hypertension was also present throughout all four


34
            pregnancies and was not attributed to pre-eclampsia.       2.    What further investigations would you perform
            There was no family history of hypertension. At the              to elucidate the cause of this patient’s labile
            time of presentation to the renal clinic her BP was              hypertension?
            164/100 mmHg, despite treatment with methyldopa
            and captopril. Her physical examination including the
            cardiovascular system was unremarkable. The results
            of the initial investigations were as shown below:

            Serum                                                                                                                   Ca
            Sodium          142 mmol/L         (135 – 145)
            Potassium       3.0 mmol/L         (3.6 – 5.1)
            Chloride        105 mmol/L         (95 – 107)
            Bicarbonate      29 mmol/L         (22 – 32)
            Urea            5.1 mmol/L         (2.9 – 7.1)
            Creatinine      61 mmol/L          (60 – 110)

            LFTs, calcium, phosphate, urate and lipids were all
            within normal limits.

            24 hr urine
            Adrenalin       0.03 μmol/day      (0 – 0.11)
            Noradrenalin    0.23 μmol/day      (0 – 0.47)
            Dopamine        3.81 μmol/day      (0 – 2.60)


            Discussion
            Question 1
            The secondary causes of hypertension are renal               I-meta-iodobenzylguanidine (MIBG) scan showed no
                                                                       131

            (parenchymal or renovascular), adrenal (cortex or          evidence of a phaeochromocytoma.
            medulla), pre-eclampsia, coarctation of the aorta and
            miscellaneous factors such as oral contraceptives and      Given the fact that approximately 20% of hypertensive
            ingestion of licorice.                                     patients have low normal serum potassium due to a
                                                                       variety of causes including diuretics, purgatives,
            On the basis of the history and results, the most          licorice, etc., a low serum potassium concentration by
            likely causes would be renovascular hypertension or        itself is not a good indicator of hyperaldosteronism. This
            adrenal causes such as phaeochromocytoma or Conn’s         patient, however, was young, resistant to anti-hyperten-
            syndrome. Cushing’s syndrome is unlikely as the            sive therapy and presented with hypokalaemia whilst
            patient did not have Cushingoid features.                  taking an ACE inhibitor, which causes hyperkalae-
                                                                       mia. She, therefore, warranted further investigation for
            In view of the elevated urinary dopamine, a dopamine-      primary hyperaldosteronism.
            producing phaeochromocytoma was suspected, but a


The Clinical Biochemist Newsletter September 2007
 Omniscience

 Discussion
 Question 2
 Plasma renin activity, plasma aldosterone concentration       left laparoscopic adrenalectomy and had an uneventful
 and plasma aldosterone/renin ratio were used as screening     recovery.
 tests.
                                                               References
 Aldosterone        403 pmol/L        (140 – 400)              1.   Nadar S, Lip G, Beevers D. Primary hyper-
 Potassium          3.4 mmol/L        (3.6 – 5.1)                   aldosteronism. Ann Clin Biochem 2003; 40: 439 – 52
 Renin-basal        3.5 pg/mL         (5.4 – 45)               2.   Law LK et al. Renin and aldosterone: clinical sig-
 Bicarbonate        34 mmol/L         (22 – 32)                     nificance and laboratory measurement. Clin
 AR ratio           115               (<25)                         Biochemist Rev 2001; 22, 3 – 5
                                                               3.   Glendenning P, Vasikaran S. Surgically correct-
 The results are indicative of hyperaldosteronism (Conn’s
 Syndrome). The diagnosis was confirmed by adrenal
                                                                    able hypertension. Pathology 2002; 34, 297 – 98
                                                                                                                         35
 venous sampling. An adrenal CT scan showed a 1 cm
 low-density focus in the left adrenal gland consistent with
 a small adenoma. The patient subsequently underwent a



Case 2           Dr. Vivienne Ellis
                 Department of Clinical Chemistry, SEALS – Kogarah Campus, New South Wales
                 e-mail: Vivienne.Ellis@sesiahs.health.nsw.gov.au



  Case History
  A 28-year-old woman (G1P0) presented at 40 weeks              Analyte             Result          Reference Range
  gestation to the labour ward complaining of shortness         Sodium              135 mmol/L      (135 – 145)
  of breath and epigastric pain associated with nausea          Potassium           4.4 mmol/L      (3.6 – 5.1)
  and vomiting. Shortly thereafter she had a seizure            Chloride            108 mmol/L      (95 – 107)
  and was attended by the arrest team. She was admitted         Bicarbonate         18 mmol/L       (22 – 32)
  to ICU following an emergency caesarean section               Urea                3.3 mmol/L      (2.9 – 7.1)
  that resulted in the delivery of a live female infant.        Creatinine          60 μmol/L       (60 – 110)
  Hypertension developed post-delivery and required             Albumin             18 g/L          (33 – 48)
  multiple antihypertensives to bring it under control.         Total Protein       46 g/L          (61 – 79)
  Despite an initially stormy post-operative period with        Bilirubin (total)   48 μmol/L       (0 – 25)
  decreasing haemoglobin, tachycardia and decreasing            ALP                 122 U/L         (38 – 126)
  urine output she recovered sufficiently to be discharged      ALT                 322 U/L         (< 45)
  10 days after admission.                                      AST                 862 U/L         (< 45)
                                                                GGT                 13 U/L          (0 – 30)
  The serum biochemistry and haematology results after          Calcium             1.84 mmol/L     (2.25 – 2.58)
  admission to ICU were as follows:                             Magnesium           1.85 mmol/L     (0.74 – 1.03)
                                                                Phosphate           1.12 mmol/L     (0.80 – 1.50)
                                                                Urate               0.45 mmol/L     (0.16 – 0.48)
                                                                LD                  1806 U/L        (90 – 200)
                                                                Hb                  104 g/L         (115 – 165)
                                                                WBC                 11.66 x 109/L   (3.50 – 11.00)
                                                                PLT                 50 x 109/L      (150 – 450)
                                                                APTT                43 sec          (25.0 – 37.0)
                                                                PT                  17.2 sec        (12.0 – 15.0)
                                                                INR                 1.5             (0.8 – 1.1)
                                                                Haptoglobin         < 0.1 g/L       (0.3 – 2.0)



                                                                   The Clinical Biochemist Newsletter September 2007
            Omniscience
 Case 2

            Continued from previous page...Blood film:                   Questions
            occasional helmet cells, spherocytes, fragments, and         1.    What is the most likely diagnosis for this patient?
            polychromasia                                                      Give reasons for your answer and discuss the
                                                                               pathophysiology of the condition.

                                                                         2.    What other conditions with similar clinical and
                                                                               laboratory features should the clinician consider
                                                                               in the differential diagnosis of a critically ill
                                                                               pregnant patient? What tests might be useful in
                                                                               differentiating them?


36                                                                       3.    Discuss the aetiology of the elevated serum
                                                                               magnesium and depressed serum calcium levels.
                                                                               If the patient developed symptoms that could be
                                                                               attributed to hypocalcaemia what method would
                                                                               you use to confirm your suspicions?


            Discussion                                                   arthralgias cutaneous manifestations will suggest SLE
                                                                         and should be followed up with appropriate serological
            Question 1
                                                                         tests.
            The most likely diagnosis is the HELLP syndrome
            (Haemolysis, Elevated Liver enzymes and Low Plate-
                                                                         Question 3
            let count) given the presence of thrombocytopaenia
                                                                         Intravenous magnesium sulphate is a recognised therapy
            (plt< 100 x109 /L), elevated ALT and AST and elevated
                                                                         for eclampsia and the patient in question received the
            LDH, bilirubin and depressed haptoglobin.
                                                                         therapy over a 48-hour period.
            HELLP syndrome is a complication or severe form of pre-      Hypermagnesaemia is a known cause of hypocalcaemia.
            eclampsia which is characterised by multi-organ dysfunc-     In vitro and in vivo animal studies have shown that high
            tion. A systemic maternal inflammatory response results      extracellular magnesium concentrations resulted in de-
            in maternal endothelial cell dysfunction leading to fibrin   creased secretion of PTH from the parathyroid glands,
            deposition and organ hypoperfusion with the development      which could induce hypocalcaemia.
            of microangiopathic haemolytic anaemia and thrombocy-
            topaenia. Reduced hepatic perfusion causes periportal or     In addition the patient has a low serum total protein (due
            focal parenchymal necrosis of hepatocytes with elevation     to low albumin). Since the major part of protein-bound
            of liver enzymes                                             calcium in serum is bound to albumin a decrease in se-
                                                                         rum albumin concentration will result in decreased total
            Question 2                                                   calcium concentration.
            A number of conditions including thrombotic thrombo-
            cytopaenic purpura (TTP)/haemolytic uraemic syndrome         A number of studies have been published in the litera-
            (HUS), systemic lupus erythematosus (SLE) and acute          ture, which criticise the use of correction formulae for the
            fatty liver of pregnancy present with remarkably similar     classification of calcium status in critically ill patients.
            clinical and laboratory features, thus posing a diagnostic   “Corrected” serum calcium was found to underestimate
            dilemma for the clinician.                                   the prevalence of hypocalcaemia and overestimate the
                                                                         prevalence of normocalcaemia in this patient group.
            If a patient has not shown signs of improvement by 72        The measurement of ionised calcium is the best means
            hours post delivery or suffers progressive deterioration     of assessing calcium status in critically ill patients.
            in renal or haematological parameters, a diagnosis of
            TTP/HUS should be considered.                                References
                                                                         1.   Clinical Critical Care Medicine (ed. Albert, Slutsky,
            Hypoglycaemia and hyperammonaemia are very                        Ranieri, Takala and Torres), Mosby Elsevier USA
            suggestive of acute fatty liver while a history of                2006; p. 628 – 30



The Clinical Biochemist Newsletter September 2007
Omniscience

2.    Egerman R, Sibai B. Imitators of pre-eclampsia        5.        Dickerson R et al. Accuracy of methods to estimate
      and eclampsia Clin Obstet. 1999; 42: 551                        ionized or ‘corrected’ serum calcium concentrations
3.    Mayan H et al. Symptomatic hypocalcaemia in                     in critically ill multiple trauma patients receiving
      hypermagnesaemia-induced hypoparathyroidism                     specialised nutrition support. J. Parenteral and
      during magnesium tocolytic therapy. Nephrol. Dial               enteral nutrition 2004; 28: 133 – 41
      Transplant 1999; 14: 1764 – 6                         6.        Byrnes M et al. A comparison of corrected serum
4.    Slomp J et al. Albumin-adjusted calcium is not                  calcium levels to ionized calcium levels among
      suitable for diagnosis of hyper- and hypocalcaemia              critically ill surgical patients. Amer J. Surgery
      in the critically ill. Crit Care Med 2003; 31: 1389             2005; 189: 310 – 4
      – 93                                                  7.        Higgins C. Ionized calcium http://www.bloodgas.




     Case 3
                                                                                                                             37
                   Sharon Corsbie and Dr Narelle Hadlow
                   Biochemistry Department, Western Diagnostic Pathology, Perth. Western Australia
                   e-mail: sharon.corsbie@symbionhealth.com


      The Central Laboratory received a call from one             The serum biochemistry results were:
      of its Regional Laboratories in Alice Springs:              Sodium         136 mmol/L       (134 – 146)
                                                                  Potassium      5.0 mmol/L       (3.4 – 5.5)
      “We have a patient with a Corrected Calcium of 1.59         Chloride       101 mmol/L       (95 – 108)
      mmol/L - May we have permission to phone the result         Bicarbonate    23 mmol/L        (22 – 32)
      through to the GP?”                                         Urea           3.3 mmol/L       (3.0 – 8.0)
                                                                  Creatinine     55 µmol/L        (30 - 100)
      Other information:
      Patient is diabetic undergoing routine monitoring          Questions
      HbA1c           7.4%              (good control <7)        1.      Comment on the calcium result.
      ACR             5.4 mg/mmol       (<2.8)                   2.      What further information would you seek and
      ? Renal Dysfunction                                                what investigations would you perform?
      FBC - Hb 117 g/L, otherwise normal


      Discussion
      Question 1                                                 Electrolytes (one week prior):
      This is a strikingly low corrected calcium and most
                                                                 Sodium               137 mmol/L         (134 – 146)
      common causes include end stage renal failure, severe
                                                                 Potassium            3.7 mmol/L         (3.4 – 5.5)
      hypoparathyroidism or spurious low calcium. End
                                                                 Chloride             102 mmol/L         (95 – 108)
      stage renal failure is excluded by normal creatinine,
                                                                 Bicarbonate          26 mmol/L          (22 – 32)
      and on questioning there is no history of previously
                                                                 Urea                 3.3 mmol/L         (3.0 – 8.0)
      low calcium, calcium monitoring or supplements,
                                                                 Creatinine           53 µmol/L          (30 - 100)
      or low PTH as would be expected in severe
      Hypoparathyroidism. The most likely possibility is
                                                                 A common cause of hypocalcaemia is EDTA
      contamination of the sample, despite the apparently
                                                                 contamination (incorrect tube collection or order of
      ‘normal’ serum potassium.
                                                                 draw, i.e. collection of EDTA before SST). Ask the
      Question 2                                                 laboratory to check the magnesium level, which would
      •   Ask the laboratory if there are previous               also be decreased if EDTA contaminates the sample.
          electrolytes results available.
      •   Enquire as to staff collecting sample: are they        Phosphate            1.0 mmol/L         (0.8 – 1.5)
          an experienced phlebotomist. In this case a new        Magnesium            0.5 mmol/L         (0.7 – 1.20)
          community nurse collected the sample.


                                                                 The Clinical Biochemist Newsletter September 2007
              Omniscience

              Repeat on a second SST/PST tube if available, if a           Conclusion
              second tube is not available an urgent recollection may      Incorrect order of draw of tubes with the K EDTA tube
              be required to confirm this critical Corrected Calcium       collected before the SST tubes. The majority of the
              result.                                                      EDTA contamination is found in the first SST collected
                                                                           with less effect in subsequent tubes.
              The results below are from the second tube collected
              by the community nurse:                                      Calcium is the most affected analyte, followed by
                                                                           Magnesium and ALP.
              Sodium          136 mmol/L               (134 – 146)
              Potassium       4.0 mmol/L               (3.4 – 5.5)         Other causes of Calcium interferences include:
                              - first collection tube 5.0 mmol/L           •    Citrate, oxalate or EDTA contamination. These

38            Chloride
              Bicarbonate
              Urea
                              103 mmol/L
                              22 mmol/L
                              3.3 mmol/L
                                                       (95 – 108)
                                                       (22 – 32)
                                                       (3.0 – 8.0)
                                                                           •
                                                                                anticoagulants all bind Calcium.
                                                                                Co-precipitation of Calcium with fibrin or lipids
                                                                                can occur with lengthy storage or freezing
              Creatinine      57 µmol/L                (30 - 100)               times.
              Magnesium       0.71 mmol/L              (0.7 – 1.20)
                              – first collection tube 0.5 mmol/L

              Notable differences between the two SST tubes
              collected are:
              Potassium       4.0 mmol/L
                              - first collection tube 5.0 mmol/L
              Magnesium       0.71 mmol/L
                              - first collection tube 0.5 mmol/L

              The Calcium result on second SST tube was 2.24
              mmol/L with an Albumin of 39 g/L and Corrected
              Calcium of 2.30 mmol/L (2.20 – 2.55).




              Omniscience Copy Deadlines
               Omniscience Schedule (2 cases/Branch/issue)


               CBN Issue             Branches                         Due Date


               Dec 2007              QLD and Tas.                     October 31, 2007
               Mar 2008              NZ and SA/NT                     January 31, 2008
               June 2008             Vic. and NSW                     April 30, 2008
               Sep 2008              WA and QLD                       July 31, 2008
               Dec 2008              Tas. and NZ                      October 31, 2008




The Clinical Biochemist Newsletter September 2007
Omniscience
 Case 4

                 Sharon Corsbie and Dr Narelle Hadlow
                 Biochemistry Department, Western Diagnostic Pathology, Perth. Western Australia
                 e-mail: sharon.corsbie@symbionhealth.com

Case History
An 88-year-old Italian woman presented with marked      Blood Cultures: Negative
general lethargy for investigation. She lives at home
alone and was increasingly unwell and becoming          Samples collected: 2 Blood Culture Bottles, Citrate,
more and more dependent on her son with worsening       EDTA and SST collection tubes.
weakness and mental cloudiness / confusion.
                                                        Questions
Initial investigations were:

Sodium            141 mmol/L        (134 – 146)
                                                        1.

                                                        2.
                                                             What possibilities could explain the hypocalcae-
                                                             mia and how would you confirm these?
                                                             What is a common cause of hypokalaemia in a
                                                                                                                 39
Potassium         2.8 mmol/L        (3.4 – 5.5)              female of this age group?
Chloride          102 mmol/L        (95 – 108)          3.   What further investigations would you perform?
Bicarbonate       28 mmol/L         (22 – 32)                What is the differential diagnosis?
Urea              6.6 mmol/L        (3.0 – 8.0)         4.   What is the likely diagnosis in this patient and
Creatinine        73 µmol/L         (30 - 100)               the appropriate treatment?
Albumin           22 g/L            (36 – 48)
Total Calcium     1.14 mmol/L
Corrected Ca      1.54 mmol/L       (2.20 – 2.55)

Hb                121 g/L           (110 – 155)
ESR               42 mm /hr         (1-40)
Plt               332x109/L         (130 – 400)



Discussion                                              Malignancy - Tumour lysis, Osteoblastic Malignancies
                                                        Acute pancreatitis - Elevated serum Amylase, Lipase
Question 1
                                                        Rhabdomyolysis - Elevated CK, Myoglobinuria
Possible causes include:
                                                        Question 2
1.? Artefact: EDTA contamination; check order
                                                        A common cause of hypokalaemia in this age group
              of tube collection, repeat on a second
                                                        is diuretic use. Drug history in this patient included
              SST if available and check magnesium
                                                        Frusemide 80 mg mane, Slow K, Risperidone, Dox-
              level. Confirm hypocalcaemia if no
                                                        epin, Citalopram and Allopurinol. There was no history
              previous history (result confirmed as
                                                        of Bisphosphonate use.
              correct).
                                                        Question 3
2. Exclude:   Renal Failure - Creatinine >
                                                        Investigations performed to clarify the cause of
              350 µmol/L, + elevated PO4
                                                             Hypocalcaemia in this patient:
              Hypoparathyroidism – functional Mg        1.   Normal Creatinine - Renal failure is excluded.
              deficiency, Pseudohypoparathyroidism       2.   Exclude EDTA contamination; check Magne-
              Vitamin D deficiency                            sium (0.57 mmol/L); repeat blood collection
                                                             organised – only SST tube collected and hypoc-
              Hungry Bone Syndrome                           alcaemia was confirmed. Note the Magnesium is
              Drug Therapy - Bisphosphates,                  still low (see table below).
              Cinacalcet, Zolendronic Acid,             3.   Drug causes of hypocalcaemia were largely
              Anticonvulsants                                excluded by clinical history.



                                                             The Clinical Biochemist Newsletter September 2007
              Omniscience

              4.       Further Investigations performed were:          2.   Decreased bioavailability
                                                                            Dietary deficiency
              Total Bilirubin     3 µmol/L          (<16)                   Malabsorption – reduction in fat absorption
              ALP                 336 U/L           (<115)                  – cystic fibrosis, coeliac disease, Whipple’s
              GGT                 10 U/L            (<36)                   disease, Crohn’s disease, bypass surgery, medica-
              ALT                 11 U/L            (<31)                   tions that reduce cholesterol absorption.
              Total Protein       47 g/L            (60 – 85)               Obesity – sequestration of Vitamin D in body fat
              Magnesium           0.57 mmol/L       (0.7 – 1.20)       3.   Increased catabolism
                                                                            Anticonvulsants, glucocorticoids, anti-rejection
              Serum protein electrophoresis was performed and               medications – bind to receptors
              showed hypogammaglobulinaemia with a possible faint      4.   Decreased synthesis of 25 hydroxyvitamin D

40            abnormal band detected in the slow gamma region.
              Immunofixation Electrophoresis of serum excluded a
              paraprotein band.
                                                                       5.
                                                                            Liver failure
                                                                            Decreased synthesis of 1,25 dihydroxyvitamin D
                                                                            Chronic kidney disease
                                                                       6.   Hereditary disorders
              Working differential diagnosis:                               Vitamin D Resistant Rickets
              Vitamin D deficiency                                           Vitamin D Dependent Rickets Type 3
              Severe hypoparathyroidism                                     Autosomal Dominant Hypophosphataemic
              Pseudohypoparathyroidism                                      Rickets
                                                                            X-linked Hypophosphataemic Rickets
              The patient was referred to an Endocrinologist and            Pseudohypoparathyroidism (end organ
              further tests were undertaken:                                resistance)
                                                                       7.   Acquired disorders
              PTH                 101 pmol/L        (0.8 – 8.0)             Tumour-induced osteomalacia
              25 OH Vitamin D     < 10 nmol/L       (>60)                   Granulomatous disorders, sarcoidosis,
                                                                            tuberculosis, some lymphomas
                                                                            Hyperthyroidism
              Question 4                                                    Hypoparathyroidism - Post-surgery, Idiopathic,
              The most likely diagnosis in this patient is severe           Magnesium depletion
              Vitamin D deficiency.
                                                                       In this patient it was felt that lack of sun exposure (re-
              The classical symptoms of Vitamin D deficiency are        maining house-bound) and poor diet caused the severe
              Hypocalcaemia secondary to decreased gut absorption,     Vitamin D deficiency.
              Hypophosphataemia secondary to an increase in PTH
              stimulated by the decreased calcium, and elevated se-    Treatment of severe Vitamin D deficiency should be
              rum ALP due to increased osteoblast activity caused by   managed by Vitamin D therapy supplemented with oral
              low calcium and Vitamin D.                               Calcium. A careful watch should be kept on the plasma
                                                                       Calcium levels because of the possibility of Hypocal-
              Although there is no consensus on optimal levels of 25   caemia.
              hydroxyvitamin D as measured in serum, Vitamin D
              deficiency is defined by most experts as a 25 hydroxy-     Reference
              vitamin D level of less than 50 nmol/L.                  Michael F. Holick. Vitamin D Deficiency. N Engl J
                                                                       Med 2007;357:266-81
              Causes of Vitamin D deficiency:
              1.  Reduced skin synthesis
                  Sunscreen use - reduces Vitamin D3 synthesis
                  Skin pigment – absorption of UVB radiation by
                  melanin
                  Ageing – reduced 7-dehydrocholesterol in the
                  skin
                  Season, Latitude, Time of day



The Clinical Biochemist Newsletter September 2007
Omniscience
  Case 5
                  Dr Sydney Sacks
                  Clinipath Pathology, Perth. Western Australia
                  e-mail: ssacks@clinipath.net



Case History
An 80-year-old woman was diagnosed with IgG lambda
myeloma in September 2003. At presentation she had                 Control
a 42 g/L paraprotein in the fast gamma region and was
Bence Jones Protein (BJP) negative. She was treated                  23/4
with Thalidomide, IV Bisphosphonate, Dexamethasone


                                                                                                                         41
and Clarithromycin with reduction of her paraprotein to




                                                                                                 
3 g/L in August 2004.
                                                            Questions
She relapsed in September 2004 and was started              1.    What are the causes of renal failure in myeloma
on Melphalan. She developed acute renal failure in                and how would you investigate these patients?
November 2004 and then commenced long-term dialysis         2.    What changes may renal failure have with respect
for CRF thereafter. Her paraprotein size reduced to 1g/L          to the SPE appearance in myeloma?
on Bortezumib and remained low (3g/L) until February        3.    The treating haematologist questioned the validity
2007 but then relapsed on 12/2/07 and responded to                of the fluctuating paraprotein levels in the table
Bortezumib, Dexamethasone and Cyclophosphamide as                 above, which did not accord with the clinical
follows:                                                          picture. What are the possible causes of the varying
                                                                  paraprotein size and how would you test for
             12/2    19/2   14/3   2/4   16/4   23/4              them?
 T Prot      81      78     63     73    65     69

 Gamma       19      16     10     12    7      13
 Globs
 Paraprot    13      10     6      9     4      8

 IgG                 17.7                8.3    7.9



Discussion
Question 1
Renal failure occurs in 20% of myeloma patients and
50% of patients have renal pathology. Hypercalcaemia
(secondary to tumour mediated bone destruction
by osteoclast activating factors) is the commonest
cause of renal failure. Hypercalcaemia causes
nephrocalcinosis and tubular damage, which in turn
can cause polyuria, dehydration and prerenal failure,
progressing to acute tubular necrosis and intrinsic renal
failure if not rapidly corrected. Tubular damage due to
uptake and consequent toxicity of excess light chains
(Bence Jones protein) by renal tubular cells is almost
invariably present. Hyperuricaemia secondary to tumour
cell lysis with intraluminal urate crystallisation and
obstruction of tubules; recurrent urinary infections due
to immunoparesis, and amyloid deposition may also be
contributing factors. Some of the drugs used may also
be nephrotoxic.



                                                                  The Clinical Biochemist Newsletter September 2007
            Omniscience


            Monitoring of urinary Bence Jones protein (even              with that of fibrinogen, and this should be borne in mind
            in patients who are initially negative as they may           in patients who are anticoagulated. Renal failure patients
            subsequently become positive), serum calcium, U&Es,          are heparinised during dialysis and on investigation our
            and urate may help early detection and avoidance of          patient had “elevations” of her paraprotein when blood
            renal complications. Onset of the Fanconi syndrome           was taken soon after or during dialysis. The fact that the
            (glycosuria, phosphaturia, renal tubular acidosis) is an     IgG level on 16/4 and 23/4 was around 8 g/L on both
            early indicator of renal tubular damage in the patient       occasions, while the paraprotein was quantitated at 4
            with myeloma.                                                g/L and 8g/L, is evidence that the paraprotein per se did
                                                                         not change in size. Note that specific immunoglobulin
            The main cause of the renal failure in our patient was       measurement significantly overestimated paraprotein

42          thought to be the development of significant BJP during      size compared to protein electrophoresis in this patient.
            her relapse in September 2004.                               This is a usual finding in paraproteinaemia.

            Question 2                                                   Fibrinogen interference in the paraprotein quantitation
            Bence Jones protein (MW 17000) is freely filtered by         was confirmed by addition of thrombin to the specimen
            the normal kidney and thus is usually only found in the      of 23/4; this caused a fibrin clot to form. The residual
            urine when using protein electrophoresis methods. As         serum had a paraprotein of 4g/L confirmed on
            about 20% of myelomas only have BJP and no serum             electrophoresis. Ensuring that the patient bloods are
            paraprotein, it is important to perform both serum           taken before heparinisation has since reliably maintained
            and urine protein electrophoresis when investigating         paraprotein size at 4 g/L.
            possible cases. Renal failure with reduced glomerular
            filtration may result in the BJP being present in both
            urine and serum.

            Question 3
            Cryoglobulinaemia should be considered when
            paraprotein concentrations are unexpectedly variable or
            absent, particularly when patients present with vasculitic
            problems and/or necrosis of the extremities. Paraproteins
            which are cryoglobulins are usually IgM, however,
            IgG and IgA paraproteins may also occasionally be
            implicated.      Demonstration of cryoglobulinaemia
            requires specimen collection, separation, storage and
            analysis to be performed at 37°C to prevent precipitation
            of the paraprotein before it can be detected and
            analysed. Cryoglobulins that only precipitate at very
            low temperatures (below 10°C) may not be clinically
            significant but may still cause analytical problems when
            samples are refrigerated. Cryoglobulins were negative
            in this patient.

            Incomplete clotting of plasma and fibrinogen co-
            migration with paraprotein: This may be very difficult
            to detect when the paraprotein mobility coincides exactly




The Clinical Biochemist Newsletter September 2007

								
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