BIORHEOLOGY, 27; 921-929, 1990 0006-355X/90 $3.00 + .00 Printed in the USA. Copyright (c) 1990 Pergamon Press pic. All rights reserved.


H.Hartert Richard-Wagner-Str. 1, 6750 Kaiserslautern,


(Accepted by Editor-in-Chief S. Witte)


Orbitaretry (Hartert) is a rreological ex-vivo rrethxJ to follOti up physical assembly of a coagulun in layers during natural intensity of flOti by orlJital rroverent. Fibrin elasticity in tre Orbitareters m::x:le of Resonance lhrarIJqJraphy is differentiated fran platelet activity as v.ell as e.g. fran tre effects of disSEminated coagulation - minimal in liver disease and rreximal during disturtJances of oolivery. Transition into tre m::x:le of dynanic TerdJgraphy (Hartert) will e.g. register all fast going tests lasting minutes or seconds. It is carparable to an accelerated farm of 1br.:rrbelastography (Hartert), tre intercourse of w,ich with coagulun yet is an exclusively static qJeration. IV10tTer category is rreasurerent of blood and plasrre viscosity. In concentrated blood it seizes plasticity of blood cells as v.ell as treir intensity of aggregation in orbital flOti. The latest rrethxJical oovelq:rrent of Orbitaretry is control of platelet activity in its function of acresion. This is realized by rreasurerent of specific physical effects released in platelet containing coagulun. They gererate a structural degradation of fibrin elasticity rnxlul as v.ell as a tendency for coagulun ad1esion. The practical use of Act-esiography is control of anticoagulants and platelet protecting substances in their quantitative influence on coagulun structure and on tre rrentioned platelet activities. A special disturabance of trese platelet depending rrechanisns obviOJSIy is getting evidence in case of v. Willebrand' s syrdrore.

Orbitometry is the endeavor to seize the functions of blood coagulation in an as natural way as possible. Principle of the method is the orbital movement of an elastically suspended cone pendulum (Fig. 1A). Its cylindrical plunger is swinging in an orbit with a self-frequency of about 38Hz. By a permanet electrical impulse it is forced to oscillate in the higher frequency of 48Hz. With a radius of about O,lmm the plunger is oscillating in a

Key words: Orbitometer, fibrin elasticity, strain of flow, nance, adhesiography, platelet shape change. 921





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FIG.l A: Orbitometer, cone pendulum (plunger) elastically suspended, orbitally moving (o,lmm radius) in cup.Circular squeezing strain is acting on filled in material contained between cup and plunger. B: Resonance-Thrombogram (RTG, Kaolin-incubated PRP) . Ascen ding leg F = strain-formed fibrin structure; descending leg P= deforming platelet activity. Dotted line: Flattened P-leg due to insufficient or missing platelets .


4 FIG:2 Elasticity attenuating deformation of fibrin structure by nor mal platelet activity . (Fig. by E.Morgenstern), (4) . f ixed cup leaving open a circular gap of lmm width between plunger and cup. Fluid blood or plasma in this gap by the mini mal stirring effect of orbital oscillation will flow around, comparable to a flow rate in a coronary artery(2,3). I.

On the non wettable surfaces of plunger and cup coagulation is

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starting layerwise, finally filling gap space with a coagulum adhering very tightly to its surfaces. The viscoelastic effects of its structure definitely are producing a special structural coordination by the feedback-strain of unidirectional movement of plunger. Registration of the correspondingly changing wideness of the plungers oscillation radius represents the so called Resonance-Thrombogram, (RTG, Fig.iB). The moment coagulum is joining plunger and cup with the first through fibrin strands the circular flow is halting and their physical effect of increasing elasticity is adding to constant elasticity of cone pendulum. This effect is competent for an additive increase of pendulum self-frequency drawing it near to driving frequency. So the first fibrin junctions start a steep rise of recorded line by growing resonance of cone pendulum due to an increase of elastic strength of coagulum, mainly depending on activity of phospholipid and factor XIII. This ascending first phase of coagulum production in RTG is followed by a second but descending phase due to intervention of platelet activity. Platelets coming into contact with the fibrin strands are changing the shape of them as well as their elasticity into a viscoelastic bulk of reduced elasticity modulo They are some kind of a break of elastic fibrin oscillation. So the steep primarily fibrininduced ascent of the graph suddenly is turned into the opposite direction by the sticky and elasticity choking platelet activity. Fig.2 (4) shows the "Karate playing" platelets and the weakened fibrin fibres. If platelet poor plasma is taken the RTG-test, the platelet generated descent is missing totally (Fig.iB, dotted line): without platelets RTG-formation will rest after the production of fibrin; the recording line nearly horizontally goes on with no indication of further coagulation activity (6,7,8). Another example for relation between orbitometric differentiation of coagulum structure and clinical disturbances of coagulation is disseminated intravascular coagulation, the fibrin monomers of which do interfere with normal fibrin structure. The insufficient strength of fibrin in a mean case of DIC is seen in Fig.3c, which here also could indicate a simple hypofibrinogenemia. In Fig.3f there in contrast is an RTG of a case with massice DIC (5). The synopsis of RTG-types in Fig.3 gives a simple survey of further basic RTG-forms as part of Orbitometry. Beneath there are opposed the corresponding Thrombelastograms (TEG), the graphs of my predecessor method (i), which is not able to give adequate informations about the physical operations of platelets. II.

Another mode of Orbitometry is tendography, a method to measure the overall viscoelastic strength of coagulum during its formating (Fig.4a). (Its looks like halfway up of a TEG, the practi-






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FIG.3 Thrombelastograms (TEG, Hartert 1951), different situations of normal or pathological blood coagulation. Corresponding RTG's are giving more extensive information and differentiation separately comprising of platelet activity as well as its feedback with fibrin structure. a = normal, b = hyperfibrinogenemia, c = hypofibrinogenemia (partially similar to OIC) ,d = thrombocytosis, e = thrombopenia, f = extreme OIC. (5)

FIG.4 a = normal TG (tendogram); citrated blood, Kaolin-incubated before recalcification. b = fast acting fibrinolysis.

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cally motionless intercourse of which with coagulation yet is not comparable to Tendography). The excitation frequency of Tendography-plunger in contrast to RTGraphy is lower than real fibrin self-frequency. Recording of Tendography for practical reasons is moved faster than that of RTG. Employment of this mode includes differentiation of all fast starting coagulation processes, yet also fibrinolysis (Fig. 4b) . The TG-test usually includes preincubation with constant surface activity by addition of Kaolin. Depending on the assay conception this preincubation may be combined with Kephalin in the sense of PTT. Depending on the choosen type of test the same is approriate for the use of RTG mode. Its recording spees usually is slower that that of Tendography. III.

Viscography is a special mode of Drbitometry with another set of plunger and cup. In the low excitation frequency of Tendography it measures plasma - and blood-viscosity as well as flexibility and aggregation of blood cells. The physical differentiation by this method to some extent is comparable to that of an Ostwald-Viscosimeter.

IV. Adhesiography (AHG), basically related to Tendography, is a new mode of Orbitometry to extend the control of physical platelet function. Platelets coming into contact with glass surface under a comparatively high physiological stress very fast will adhere to it and in a very active change of form spread their surface contact. The basic logic of this adhesion process in vitro is, that also fibrin generally has a high tendency to adhere to surfaces. Platelets on the other hand in comparison to fibrin will only get in direct contact, if there aro no platelets having had priority in occupation. If platelets have occupied such a wettable surface, fibrin will come after and stick to the platelets. Yet finally the tightness of adhesion of the weak platelets is lower than that of rigid fibrin, also in case of a wettable surface as glass. So any stress of tension will extra vivum loosen a coagulum the sooner, the more it is adhering primarily by platelets and not directly by fibrin. The surface-stimulated and fibrin deforming activity of platelets will penetrate a coagulum fast and completely, if its range is shallow and - as in the mode of AHG - if coagulation is initiated in a situation of flow. Fig.5a is a typical normal AHG of a normal platelet rich plasma (PRP) from citrated blood, spontaneously sedimented, recalcified. After the descent of recording indicating the first fibrin oroduction, it shows its



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c d

e FIG.5

a= normal AHG (Adhesiogram), b = ASA-therapy. Marcumartherapy: c = Quick 21%, d = Quick 12%, e = Quick 8% .


Pentoxifyllin-therapy. Left = normal reaction, right: with slight platelet check.

sudden return up to basic line by the most intensive fibrin deforming platelet activity. The latter is due to the proper function of platelets throughout coagulum, producing homogeneity of the fibrin-platelet-bulk and by that reducing elasticity modul of the viscoelastic coaaulum. This reduction is co-

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FIG.? v.Willebrnnd-Syndrom, clin. moderate; 60 min after blood collection (a); 120 min later (b). Patients daughter, clinically unmolested (c). inciding with the consequence of increasing resonance as well as increase of orbital radius forcing an ascent of recorded line by this mollifying platelet activity. So a steep inversion of recorded line is caused, surmounting finally basic line. Smooth recording of ascent will show an immaculate adhesion of the viscoelastic coagulum to the wettable glass surfaces of AHG set. If the adhesive capacity of platelet is reduced, coagulum will be teared off the wettable surfaces the more the radial amplitude of orbital movement is widened, consequently increasing tractive power. Fig.5b shows test with plasma of a patient under therapy with ASA. The recorded line in its upper ascending part is passing with only one tear off, otherwise with some reduced steepness by decreased platelet activity to weaken fibrin structure. Fig.5c is an AHG from a patient taking Marcumar (Quick-value 21%). The ascent breaks and turns sooner off, indicating a more intense deterioration of platelets compared with Fig.5b. In Fig. 5d there is a test of another patient under same therapy but with a quick of only 12%. The delayed coagulation process is retarding fibrin production, yet coincidently the integrating platelet activity is not only slowed down but generally deminished. There is left an only minimal platelet dependent ascent. Some irregularity in the horizontal part of ascent line is due to a comparably small tear off activity in this lower range of orbital movement. It means that platelet function in this kind of anticoagulative therapy is reduced in its own special sense, yet apparently not generally parallel to grade of Quick-value reduction. The last stage of Marcumar-effect is an example of AHG made from PRP with a quick-value of 8% (Fig.5e). Here the anticoagu-



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lant tendency to decrease more and more the platelet born second phase ascent in the AHG figure went to the extreme of a total disappearance of any kind of figurative second phase. So the AHG looks like a normal Tendogram (Fig.4a) not mentioned the prolonged coagulation time. First tests with low dose heparin show a type of AHG reaction resembling that of Marcumar, but related to coagulation time with a lesser damping of platelets shape change activity. Fig.6 shows two AHG's of patients taking Pentoxifyllin. The form of left graph resembles a normal AHG, indicating that coagulation and platelet activity are rather unchanged. The right AHG is obviously broadenend, marking a process which minimally diminishes deformability of platelets and likewise the normal tendency to weaken elasticity of coagulum, whereas tightness of coagulum adherance is unchanged. Also in other tests with this substance there was no tendency of coagulum-loosening. To evaluate more of the role of platelet activity in the complex process of Adhesiography, a test was made with PRP from a patient suff 3ring from Thrombasthenia Nageli-Glanzmann (120000 platelets/mm ) ,the platelets of which are defective in their acitivity e.g. to produce clot retraction. An AHG was recorded, which practically had the shape of the just described Tendogram in Fig4a. This simply means, that any AHG-figurechanging effect of platelets, as seen in a normal AHG, here was missing totally. The behaviour of coagulum was comparable to an AHG recorded with a very platelet poor plasma. So also here any kind of graph-change in the sense of platelet intended secondphase-ascent in the AHG was missing. The impotent platelets in thrombasthenia on the other hand are leaving enough space for a direct contact of fibrin with unoccupied glass surface. So also in presence of defective platelets fibrin apparently will adhere very tight to glass of AHG-set. Fig.7a is the AHG of a patient with a clinically moderate form of v.Willebrand-Syndrom, 90min after collection of citrated blood sample. Following the three times prolonged coagulation time there is only a short indication for launching platelet activity. But 180min after blood collection the sample (Fig.7b) with its platelet depending ascent - in spite of the still twofold coagulationtime - is getting some normality, at least regarding platelet activity. The blood of the patients daughter (19 years old) because of no striking clinical signs not yet was investigated. The AHG (Fig. 7c) of her sample (PRP from spontaneous sedimentation as in mothers test) shows a defect in platelet activity, combined with a normal coagulation time. To comprise.: The AHG-mode is a control of platelet behaviour during coagulum production with regard to the integrated role of wettable surfaces in coagulation adherance as well as on the role of platelets molding the ascent figure. It has opened some new biophysical aspects of platelet function. A longer period of clinical application as well as differentiation of the bio-

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chemical background will be useful for more understanding. The Orbitometer in its type of series production is easily transposable into the modi of Resonance-Thrombography, of Tendography, of Adhesiography and of Viscography - simply by changing the special sets of cup and plunger as well as of velocity of inducement (Producer Heinrich Amelung GmbH, Lehbrinksweg 59, D-4920 Lemgo 1).

REFERENCES 1. HARTERT,H.: Die Thrombelastographie. Eine Methode zur physikalischen Analyse des Blutgerinnungsvorganges. Z.f.d.ges.experim.Medizin, 117, 189-203, 1951. 2. HARTERT,H.: Resonance-Thrombography, theoretical and practical elements. Biorheology 18, pp.693-701, 1981. 3. HARTERT,H.: Poiseuille Award Lecture. Biorheology in the practice of Medicine: Resonance Thrombography, Biorheology 21, 19-32, 1984. 4. E.Morgenstern,U.Korell und J.Richter: Platelets and fibrin strands during clot retraction. Thrombosis Research 33; 617623, 1984. 5. HARTERT,H.: Differenzierung der Therapie von Gerinnungsstorungen durch Diagnostik mit dem Resonanzthrombographen, Therapiewoche 36, 4626-4634, 1983. 6. HARTERT,H.: Der Gerinnungsfaktor XIII als strukturbildendes Element in der FrUhphase des Resonanz-Thrombogramms. Verh. Ber.4.Kongr.Dtsch.Ges.f.klin.Hamorheologie: "Hamorheologie u. Hamatologie". S.172, 1985. 7. HARTERT,H.: Ein direkter Effekt von Thromboplastin auf die Fibrinformation im Resonanzthrombogramm. In:Rationelle Therapie u. Diagnose v. hamorrhagischen u. thrombophilen Diathsen. Hrsg.E.Wenzel,P.Hellstern,E.Morgenstern,M.Kohler,G.v.Blohn 6.60, 1986. 8. HARTERT,H.: Fibrin Elasticity and Coagulation. Biorheology 25; 137-145, 1988.

Orbitometer flow and thrombus formation.

Orbitometry (Hartert) is a rheological ex-vivo method to follow up physical assembly of a coagulum in layers during natural intensity of flow by orbit...
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