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									                        RADIOISOTOPE                                        KNEE             JOINT                     SCANS                    IN       HAEMOPHILIA
                                                                    AND             CHRISTMAS                                  DISEASE

         CHARLES          D.     FORBES,                 WILLIAM             R.     GREIG,           COLIN               R.      M.        PRENTICE,                 GLASGOW,                      ScoTLANI,


                                                               GEORGE             P. MCNICOL,*                          LEEDS,             ENGLAND

                                     From          the     LJnilersitv         Departineizi           of Medicine,                   Glasgow            Royal         Infirmary

            As early           as I 892                     s
                                                   K#{246}nighowed                   that        the recurrent                    haemarthroses                            of haemophilia                         resulted
in        progressive            joint         destruction.                        This          aspect           of      haemophilia                          has         been          studied             by      many
investigators                  (Freund               1925;          Key        1932;            Collins            1949;             DePalma                   and          Cotter           l956b;            Marion,
 Favre-Gilly,              Picault           and         Gauthier            1965).         Observations                      have         also been             made             ofjoint          abnormalities
in        haemophilic               dogs            (Swanton                 1957,          1959).               Nevertheless,                         there          is     still       doubt              about         the
mechanisms                  underlying                    the      acute          and       chronic              joint          changes.                     In acute                haemarthrosis                       it is
thought    that bleeding         starts in the synovial      and subsynovial        tissues    of the villi with formation
of sInall haematomata,              which  become     confluent    and rupture          into the joint       cavity   to produce
the sudden       severe      pain and immobility       (Swanton     1957, 1959).          Likewise      it is thought     that it is
recurrent    intra-articular        bleeds which lead to chronic       arthropathy,          hypertrophv        ofthe   synovium
and         adherence              of adjacent                    villi      progressing                  to produce                   joints            with          a thickened                    hyperaemic
synovium                 and        fibrosis   of                 the        subsynovial                   tissues.                  After             these          changes      are                 established
degenerative  changes      occur                                  in the adjacent     cartilage     and bone.
       We have investigated                                     the changes       in acute      and chronic   haernophilic                                                              arthropathy                  using
radioisotope                joint           scanning.                 Intravenous                  technetium                     (9ImTc)              with          a half-life                 of six hours                 is
an ideal isotope     forjoint    scanning    (Laneet                                              1968)         and has been used to study                                           otherjoint            diseases.
The scans,     which     consist    of a pictorial                                              image           of the isotope  localisation                                          in and           around        the
joint,         show        changes             in regional                   blood          flow          at the              time         of study              and          are        abnormal                   during
acute inflammation          (Weiss,                              Maxfield,    Munson        and Hidalgo     1965, 1966; Whaley,         Pack,                                                                       Boyle,
Dick,       Downie,    Buchanan                                 and Gillespie      1968;      McCarty,    Polcyn    and Collins      1970).                                                                         While
visualisation       of the isotope                                in an inflamed      joint     reflects mainly   increased    vascularity                                                                          of the
synovial            membrane     and otherjoint                                tissues           (Alarcon-Segovia,                              Trujeque,                  Tovar         and       Adame             1967;
Whaley             et a!. 1968),   part of the                               localisation                 of      the         radioactivity                    may           be      due         directly           to    the
synovium                 binding             the         technetium                 (Green           and           Hays              1969;             McCarty,                   Polcyn,            Collins             and
Gottschalk                 1970;  Mowat,     Disney     and Vaughan        1971).      For these   reasons                                                                                   joint        scans    are
abnormal                 in a variety    of inflammatory      joint   diseases,      such as rheumatoid                                                                                        arthritis,       gout,
psoriatic             arthritis,  acute pseudo-gout       and experimental        synovitis,  but are not                                                                                  characteristically
specific for               one type of inflammatory   change.                                                    Nevertheless,                         as McCarty                       and his colleagues
have shown,                  the joint scan may be much     more                                                 abnormal                       than      the degree                     of symptoms      and
signs         would         suggest,               and         because            they      can      be         repeated              at        intervals             and          do       give      an       index          of
blood          flow       in a joint,          we thought                    it might            be helpful              to use joint                   scanning               to measure                   the extent
of the         synovial            lesion          in the         joints       of haemophiliacs.                               In addition                     we have               compared                the      scans
taken           during           acute              haemarthrosis                        with        those              taken              in        quiescent                chronic                haemophilic
arthropathy.         Other     assessments                                    included       the scan abnormalities        in relation   to the number     of
previous     bleeding      episodes     and                                to the clinical       assessment    of the joint abnormality.       The present
study was confined           to the knee                                   joints,     where    scanning    is optimum       for clarity  and comparative
                                                           *    Professor          of Medicine,                Leeds       General              Infirmary.

468                                                                                                                                   TIlE        JOURNAL             OF     BONE          AND      JOINT SURGERY
                               RADIOISOTOPE                        KNEE         JOINT            SCANS              IN     HAEMOPHILIA                        AND          CHRISTMAS                       DISEASE                              469

                                                                          METHODS                        AND             PATIENTS                     STUDIED
          To            obtain             the       knee-joint                  scans,               five      millicuries                    of     technetium,                       as      sodium                  pertechnetate
(NaTcO4),                      were          given          as a single               bolus   intravenously                                 to each                patient   and the knee-joint      scans
commenced       twenty-five       minutes                                            later as suggested                                 by Whaley                   and his colleagues.      The image
of the radioactivity        distribution                                               in the joint      was                            obtained                  using    a rectilinear scintiscanner
(Selo Model                      DS4/4)       which has two five-inch detectors.       Scans were performed      of both    knees,
first in the                   antero-posterior       and then in the lateral    position.   The display    was in colour,      the
line spacing                    and the scan speed being adjusted         for each patient,     joint and position.      The time
taken             for       each           knee       was          approximately                             fifteen           minutes.
             Thirty-five                   patients   in this study,
                                                               were           included
                                                                             ranging     in age from     eleven                                                                                                        to sixty            years,
and     informed       consent   was obtained     from       all parents        or subjects.    Twenty-eight                                                                                                             had classical
haemophilia          and seven     had Christmas        disease.        There     was no clinical      evidence                                                                                                          of any other
variety      ofjoint     disease  and the anti-nuclear           factor    and Rose-Waaler         tests were                                                                                                          negative.
             Classification                       of the clinical                   severity                 of haemophilia                          was described                       by Biggs              and           Macfarlane
(1962).                  Patients              were          graded             as “severe”                         cases         if they             had         suffered               repeated                  haemarthroses
with              serious             crippling                and           deep              tissue           haemorrhages                            from           little            or          no        provocation,                         as
“moderate”                          cases           if they            had           sustained                      few         haemarthroses                          with              no          serious                crippling               or
occasional                     muscle               haematomas,                         and           as “mild”                  cases              if they         had           no         haemarthrosis                          or other
spontaneous                          bleeding                and merely    gave a history    of abnormal                                                                bleeding     after                         definite injury.
Thus     eighteen                       of our               patients  were classified   as “severe”,    six                                                           as “moderate”                                and eleven      as
“mild”      cases.
             In      each            patient           specific              clinical             assessment                     of      the         knee         joints           was          carried                out         and       each
of     the          features               was        arbitrarily                graded                 from             0-3     ; these              features             were              pain,         effusion,                 pyrexia,
crepitus                 and         degree           of contracture.                             This              we have              called             the     “signs               score”.                The           number                of
previous                 bleeding                 episodes            into       the       kneejoints                      was         also         graded         0-3, a score ofO recording
no       previous                  haemarthrosis,                         1 one           haemarthrosis,                         2 less               than one haemarthrosis       per year and
3 more                  than         one          haemarthrosis                      per          year;             this       we have                 called the “incidence    score”.    Six of
the       thirty-five                     patients            were            seen             with          acute             haemarthroses                         on          a background                                of     previous
episodes                 ofjoint               bleeding,              and        fifteen              with          chronic            joint          disease          of varying                      degrees                of severity.
At the              time          of examination                          two        patients                 had          subacute                 disease         ; this         category                  was            defined             as a
swollen,                 non-tender                   joint          with        a normal                      range            of movement                        which               had           not       been           the        seat       of
an       acute              bleed           for      at      least        six       months.                     Twelve                 patients              gave           no         previous                history                of joint
bleeds              and           had        normal             knee            joints            on         clinical            examination.                          In         six        of the            patients                  clinical
examination                          and          scanning             was          repeated                   as      they       recovered                   from           or         developed                      an     acute         joint
             The          radioisotope                      scan       colour   images    were                                 examined   by one observer      (C.                                             D. F.). Various
classifications                    of the                 images           were considered,                                     but it was ultimately     decided                                                that the most
practical                 method                  should             be simple                   and          visual.             Accordingly,                        the         group               of scans                    from       each
knee          joint            was         examined                and        then             said      to be normal                          if it were             obviously                      similar                to knee         joint
scans             from            controls             in     other            studies                (group             0). In the normal                                 knee scan there   is very little
isotope                 uptake.                If the         scans          were          obviously                     abnormal  in width,                                depth and degree    of isotope
uptake,                 with         or without                 irregular                 localisation,                        they      were           said        to be very                       abnormal                     (group            3).
Very          abnormal                      scans           show         a high            isotope                  uptake.             Scans            which             were          obviously                     abnormal                 but
not grossly                       so were counted    as grade  2. Slightly                                                            abnormal                 scans         were              grade           I   .        Examples                of
these scans                       are shown  in Figures    1 2 and 3.                      ,

Acute              haemarthrosis                      (Table             1)-Each                      of the           six patients                   in this         group               had          severe               haemophilia
and in each instance          the                               scans of the acutely                                    affected               knee joint              were grade     3. Serial scanning
of these    patients     showed                                   that despite   rapid                                   resolution                of the             acute  haemarthrosis       following
appropriate       haemostatic                                   therapy,    the scans                                  remained                 abnormal                for several    weeks   and in one

VOL.         54 B,          NO.      3,     AUGUST            1972
470                                C.      D.     FORBES,                W.    R.      GREIG,               C.       R.     M.       PRENTICE             AND       G.       P.    MCNICOL

patient   were still abnormal                                        at three months.                                      Lateral             scanning           of the             knees            failed     to localise
the isotope   to any particular                                        part of the joint.
Subacute             joint        disease              (Table             11)-Both                    patients                (Cases             7 and      8) had                grade             3 scans      only       in the
affectedjoints.                Both received                              haemostatic    therapy                                    and in a few days thejoint  swelling subsided,
the “sign”               score falling from                              0 : 9 to 0 : 1 in Case                                    7 and from 6 : 1 to 1 : 1 in Case 8. However,
in    Case         8 the scan               remained                 abnormal                     six weeks                  later,           the score         having             fallen           from       3 : 0 to 1 : 0.
This       patient           has          chronic             arthropathy                         and        the          score         may        represent               a baseline                  state     for      him.


                                                                                                                     FIG.        1

                                                   FIG.          2                                                                                                            FIG.        3
      Technetium             scans         of    the      knees          showing            the     spectrum                of abnormality                of the      scan         and        the    method      of     scoring.
      Figure       I-Scan            from         Case       8 showing               a grade            3 scan            in the      right     knee.      Figure     2-Scan   from                      Case  10 showing
      a grade        2 scan          in    the     right         knee.        Figure              3-Scan              from   Case               2 showing         grade I changes                       in the right   knee
                                                                                      and         grade          3   changes     in            the left.

Chronic             joint         disease              (Table              111)-The                       details            of the             fifteen         patients             (Cases             9 to 23)            in this
group           are shown.                      Eleven            ofthe            patients             had          a severe             grade         ofhaemophilia                          and      four     a moderate
           All      the     patients   had abnormal         scans from one or both knees           but the abnormality            grade
of      the      scans       did not correlate      with either     the number     of previous      bleeding     episodes       or with
the clinical              grading    of the joints.     For example,      as Table   III shows,     there were joints         in which
the scans                were grossly     abnormal       (grade   3) despite   no previous      history      of haemarthrosis           or
abnormal                  signs           in the         joint.
No       detectable               joint          disease             (Table            IV)-The                        data           of the        twelve           patients              (Cases              24 to 35)            who
had no detectable     disease                                        are shown.                            Eleven  of the twelve                                  patients had a mild     degree      of
haemophilia.      The    single                                       patient   with                        a moderate    degree                                 had been    afflicted with    severe

                                                                                                                                                    THE     JOURNAL               OF      BONE         AND     JOINT       SURGERY
                          RADIOISOTOPE                          KNEE        JOINT            SCANS            IN    HAEMOPHILIA                      AND          CHRISTMAS             DISEASE                           471

paralytic           poliomyelitis                       as a child            and              had never borne                          weight      on the joints     of the lower                                   limbs;
however,                 he      had           sustained                multiple                other  bleedings                         consistent      with     this degree   of                                   defect.
Despite            the         absence            ofjoint               signs,          four          of the         patients              had       abnormal              scans         (grade                2 or 3).


          One        of the              earliest,              most         frequent                 and          most        disabling              manifestations                     of haemophitia                        is
acute        haemarthrosis,                          the        kneejoint                   being           most      frequently                  affected          (Ghormley                     and1948, Clegg
Fonio    and                   Buhler    1952, DePalma                                      and Cotler                1956b,              Jordan              1958,      Webb           and Dixon   1960).
Haemorrhages                        into the joints   start                                  to appear               as soon               as the            child      begins          to walk and Kerr

                                                                                                             TABLE             I
                                                     THE F1NDING                    IN SIX PATIENTS                      WITH ACUTE                HAEMARTHROSIS

                                                                                                     Incidence          of
                                   Case                 Age                         .               bleeding         score                 Slns    score              Scan
                                 number            (years)                  even        y          ____________                       ---______________________
                                                                                                    Right            Left                Right        Left      Right                   Left

                                         1               24                Severe                       3                 3               I I                 4           3               0

                                       2                   17              Severe                       3                 3                4                12            1                   3

                                       3                   14              Severe                       3                 3                0                  8           0                   3

                                       4                   22              Severe                       3                 3                 3               11             1                  3

                                       5                   30              Severe                       3                 3                4                 12            1                  3

                                       6                   60              Severe                       3                 3               12                  4           3                   2

                                                                                                             TABLE            II
                                                  THE           FINDING          IN Two              PATIENTS            WITH SUBACUTE                  JOINT DISEASE

                                                                                                      Incidence         of
                                   Case                 Age                                          bleeding        score                Signs      score                      Scan
                                 number            (years)
                                                                                                     Right           Left              Right            Left           Right             Left

                                       7                   14           Moderate                        0                 1                0                 0            0                   3

                                       8                   21              Severe                       3                 2                6                  1           30

(1963) has shown     that 80 per cent of children     under ten years of age with severe                                                                                                                  haemophilia
have abnormal    knee joints.   The etiology    of these changes   is poorly understood,                                                                                                                  but the joint
changes             seen in haemophilic                                      dogs            (Swanton      1957,                        1959)  are similar    to those  in humans
(DePalma              and Cotter 1956a).                                   In our            study all patients                         who presented    with acute haemarthroses
had         radiological                     evidence             of chronic                  degenerative                    joint        disease            as a result          of multiple                    previous
acute   haemarthroses.                               As the study      demonstrates,       the scan abnormality                                                                    particularly       matches
the clinical    severity                         in acute haemarthrosis.          However,     with appropriate                                                                 therapy       the joint   signs
resolved             within                  forty-eight                  hours,             but        serial           scans          remained                  abnormal              for             several       weeks
suggesting                 a persistent                    increase              of the             local      synovial                blood         flow         throughout              the            knee.
            The      etiology                  of the           signs       in the joint                      in acute             haemophilic                    haemarthrosis                         is not      known,
but it has been     suggested       that   pain   is due                                                            to     capsular                 distension      and                that         intra-articular
bleeding  will continue       until    the intrasynovial                                                                  pressure                exceeds      that   of               the         capillaries            and
arterioles               of the              bleeding             site.          The          signs          are     those            of acute             inflammation                  and             are      probably
the       result          of free              blood            in the        joint            cavity.              Free           blood           is probably                 influenced                  by articular

VOL.        MB,          NO.     3,    AUGUST               1972
472      C.       D.    FORBES,           W.      R. GREIG,              C.    R.    M.     PRENTICE              AND        G.    P. McNICOL

                                                                         TABLE             III
                       THE FINDING              IN FIFTEEN              PATIENTS           WITH    CHRONIC               JOINT     DISEASE

         Case             Age             Severit                bleedingscore                      Signs        score                     Scan
       number           (years)
                                                                 Right              Left          Right            Left          _Right_           Left

              9            24              Severe                   I                 3              0               4                2              3

          10               25         Moderate                      2                 0             4                    0            2              0

          11               21         Moderate                      1                 0              1               0                2              2

          l2                   I9Severe                             3                 3              1               2                3              3

          13                   12          Severe                   3                 3             0                    1            3              3

          14               48         Moderate                      2                 2             2                2                2

          IS               24              Severe                   3                 3             2                4                2

          :                :          Moderate                      2                 2             0                    1            I

          19               38              Severe                   3                 3             2                4                2

          20                   14          Severe                   1                 3             2                3                2              2

          21               29              Severe                   2                 3             0                4                0              3

          : :: :::::::                                                                                                                               3


                                                                         TABLE             Iv
      THE FINDING               IN TWELVE             PATIENTS          WITH     NO CLINICALLY                  DETECTABLE            JOINT       DISEASE

                           49               Mild                   0                 0              0

         25                16                  Mild                 0                0              0                0               0               0

         26                50                  Mild                 0                0              0                0               0               0

         27                II                  Mild                 0                0              0                0

         28                II                  Mild                 0                0              0                0                3              3

         29                14                  Mild                 0                0              0                0                3              3

          30               35               Mild                    0                0              0                0               0               0

          31               52         Moderate                      0                0              0                0               0              0

         32                31               Mild                    0                0              0                0               0               0

         33                14               Mild                    0                0              0                0               0               0

         34                16               Mild                    0                0              0                0               0               0

         35                34               Mild                    0                0              0                0               0               0

                                                                                                          THF     JOURNAL            OF    BONE      AND    JOINT   SURGERY
                            RADIOISOTOPE                    KNEE          JOINT          SCANS              IN 1-IAEMOPHILIA                       AND      CHRISTMAS                     DISEASE                           473

cartilage               with     release  of polypeptide                                      kinins   (Moskowitz,         Schwartz,     Michel,                                                       Ratnoff      and
Astrup                1970)    through    the conversion                                      of plasma     kallikreinogen         to its active                                                     form,     plasma
kallikrein.                 It is thought    that kinins                                    may then induce         many     of the phenomena                                                           observed      in
inflammatory                      reactions               (Ratnoff               1966).
           In        experimental                  studies           injection                 of     blood            into       the joints               of animals                   (Key          1929,          Young
and Hudacek      1954, Trueta    1966) produced        an inflammatory                                                                                    response        with hypertrophy        of
the villi.  The effect of a single      injection  was short     lived but                                                                               more      pronounced      effects  could
be produced     by multiple    injections.        A similar    histological                                                                                 picture      to that   produced       in
experimental        animals    has been found    in thejoints                                                               ofa haemophilic      patient                                 (Key 1932).   These
changes      remain      as long as blood     or excess       fluid                                                          is present.    Ambulation                                     at this time may
result           in crushing                   of some              of these               villi,          which           may          then       produce               further               bleeding              and       so
initiate             a vicious            circle.            The          fact      that            the      scans          remain             abnormal              some           time          after        all acute
clinical              features            have           disappeared                      shows               that         temporary                 synovial               hypertrophy                        is partly
involved               in the          process.
     The subacute     classification                                     represents                        a variation               of the processes                      seen in the acute joint.
In both  our patients      (Table                                    II) there      had                    been no               clinical  evidence                      of recent  acute   bleeding
and the joints                        had been swollen,                       hot and painless                              for over            twelve   weeks.    However,  the                                       scans
were identical                        with those seen                       in acute bleeding.                               Repeat             scanning    in Case 8 six weeks                                         later
showed                only       slight          improvement                       despite                total       clinical          resolution                with          adequate               haemostatic
       All            the      patients            with         chronic            joint            disease           had        abnormal                scans.            However,                   there      was         no
correlation                   between              the       number                of previous                       bleeds,         the        clinical           signs          and          the      scan         ; some
patients  with no signs in one joint                                                      had a grossly                       abnormal    scan (Cases      1 1 and 23).    Only
two of the thirty knee joints scanned                                                      in this group                      were normal    ; one of these patients    had no
signs        but had a history                             of previous                    acute           haemarthroses                        (Case   21).  None                         of the patients                      in
this       group   had a history                             of recent                   acute            haemarthrosis,                        so the abnormal                           scans  presumably
represent               a chronic                state       in which                  there          is increased                  vascularity              in the              synovium.                    This         is in
keeping    with    many    previous                                    descriptions   of the histology       of these    chronic    joints     in which
the synovium        was found       to                                be markedly     thickened,    hyperplastic      and endowed          richly   with
vascular   channels     (Bokelmann                                       1881 ; Konig    1892; Freund      1925; Collins       1949; DePalma        and
Cotler               1956a;           Rodnan,              Brower,               Hellstrom,                   Didisheim                  and       Lewis           1959; Marion                         et a!. 1965;
Trueta                1966).             Storti,           Traldi,               Tosatti              and        Davoli                 1969        have           described    a                     hypertrophic
angiomatous                      type       of synovium                     with         thin-walled                   varicose            veins         on the           surface              which          bled      even
when         touched   with a gauze                                swab.
           In the group    of patients                              with          no clinically                   detectable               joint         disease          and       no previous                  history
of bleeding                   into       the       knee         joints,           four         patients              had       bilateral            abnormal                    scans.           These          patients
were       the youngest                     in this         group.               The      abnormal                   scans        presumably                 are a reflection                        of subclinical
bleeding               into the joints, a condition                                        analogous                   to the asymptomatic                             bleeding                  from the              renal
capillaries               which we have previously                                         described                  in mild haemophilia                            (Prentice,                  Lindsay,              Barr,
Forbes,        Kennedy,      McNicol                               and Douglas                      1971).
           In those patients     with                             no apparent                   joint    disease                  the      articular          scan          may           be of value                 in the
early   detection    of joint disease, and                                                 in the acute      and                        subacute     group                      the persistence                   of the
abnormality       in the scan may indicate                                                    the importance                             of prophylactic                          therapy    with                plasma
concentrates        as suggested                                  by several   authors    (Ahlberg   1965 ; Kasper,                                                        Dietrich              and Rapaport
1970;      Brinkhous,      Carnoy                                   and   Shermer      1971 ; Hirschman,     ltscoitz                                                        and               Shulman    1970;
vanCreveld                     1971).
           It seems               certain           that          if prophylactic                          therapy             in haemophilia                       is to          be      of value,                 then       it
must            be     started           before           joint       disease              becomes                   established.                  We       feel         that       the         abnormality                  of
the articular                    scan is the earliest                        index          of synovial      hypertrophy,                              and if detected     at this                               stage          it
may    enable                    us to break      the                       vicious           circle    phenomenon                                  of joint  haemorrhage-synovial
hypertrophy-further                                 haemorrhage.                            If adequate                       long         term          therapy            can           be     given,          healing

VOL. 54 B,              NO.      3,     AUGUST           1972
474                                               C.       D.     FORBES,                     W.       R.      GREIG,                 C.     R. M.          PRENTICE                     AND          G.     P. MCNICOL

could     proceed,    perhaps    with resolution       of the synovial      changes.      if prophylactic        therapy       is
attempted       when there is established     bone disease    the results are poor (van Creveld,          Hoedemaeker,
Kingma        and Wagenvoort        1971).
        Recently,    synovectomy       has been carried      out in patients         with chronic     haemophilic        joint
disease     (Storti   et a!. 1969).       The preliminary      results   seem encouraging          but as yet no long
term follow-up     is available.  The articular                                                                               scan should                           prove of value in the selection                                                    of patients
for this operation     and in the assessment                                                                                of the short                          and long term results.    Articular                                                    scanning
may            also              prove                    of value                       in        the         assessment                           of       steroids                 and            antifibrinolytic                          agents             in the
treatment                        of acute                       joint             bleeds.


I    .    in      thirty-five                             patients,                      twenty-eight                           with           classical                haemophilia                          and         seven           with          Christmas
disease,                   arthropathy                                  of        the          knee            of        various                  grades                has          been             investigated                      by       radioisotope
scanning       after intravenous                                                         injection                  of technetium,                             99mTc.
2. The abnormality               of                                                the       colour                  scan particularly                             matches                           the       clinical                severity           in       acute
3. in patients    with no clinically                                                                        apparent                   joint             disease             the         scan          may          be of value                      in the         early
detection  of involvement.
4.        The              possible                       value              of articular                         scanning                      in the               selection                  of         patients              for          treatment                and
in the            assessment                                   of the              short             and          long          term            results              is discussed.

AHLBERG,                    A. (1965):                         Haemophilia                         in Sweden.                   VII Incidence,                       Treatment                 and          Prophylaxis                ofArthropathy                      and
          other                 Musculo-skeletal                                   Manifestations                          of         Haemophilia                       A      and        B.           Acta         Orthopaedica                      Scandinavica,
          Supplementum                                    77.
ALAR#{231}ON-SEGOVIA,                                    D.,      TRUJEQUE,                    M.,          TOVAR,              E.,        ADAME,            M.      A.      (1967):            Scintillation                Scanning             of Joints            with
          Technetium                              99m.            (Abstract)                   Arthritis             and         Rheumatism,                      10,       262.
ANON (1968):                           Editorial.                      Lance,’,               2, 131.
BIGG5,            R.,           and               MACFARLANE,                            R.      G. (1962):                     Human               Blood            Coagulation                     and      its Disorders.                     Third           Edition.
          Oxford                 : Blackwell                          Scientific              Publications.
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VOL. 54 B,                   NO.         3, AUGUST                        1972

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